CN105816513A - Medicine for treating coronary microvascular dysfunction and preparation method thereof - Google Patents
Medicine for treating coronary microvascular dysfunction and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a medicine for treating coronary microvascular dysfunction and a preparation method thereof .The medicine is prepared from 30 g of milkvetch roots, 15 g of radix angelica sinensis, 12 g of rhizoma chuanxiong, 10 g of radix ginseng and 6 g of radix notoginseng powder .The medicine can be applied in the convalescence of a coronary heart disease, myocardial ischemia, stable angina pectoris and myocardial infarction .Pharmacological research shows that the medicine can effectively relieve myocardial oxidative damage and myocardial inflammations, dilate coronary vessels, improve myocardial blood supply and blood flow distribution, enhance the myocardial contractility, improve microcirculation, enhance the myocardial functions and reduce myocardial cell apoptosis to effectively relieve various symptoms of the diseases, improve the life quality of patients and improve the exercise capacity of the patients .Compared with same kinds of medicine, the medicine has the advantages that all the medicinal materials are combined, both symptoms and root causes are treated, and the effects of benefiting qi, promoting blood circulation, dispersing blood stasis and dredging the collaterals are achieved .The medicine can promote blood circulation to remove blood stasis and invigorate qi and blood.
Description
Technical field
The invention belongs to medical formulation field, particularly relate to a kind of medicine treating arteria coronaria Microvessel Dysfunction and preparation method thereof.
Background technology
Coronary artery generation atherosclerotic lesion and cause lumen of vessels stenosis or occlusion, cause myocardial ischemia, anoxia or heart disease that is downright bad and that cause, be referred to as " coronary heart disease ".Along with growth in the living standard and the change of rhythm of life, cardiovascular disease is significantly increased, and becomes the chief complaint that threat human health, particularly middle-aged and elderly people are healthy.Coronary heart disease, because of features such as its " sickness rate are high, disability rate is high, mortality rate is high, relapse rate is high, and complication is many ", has caused the great attention of extensive patients and medical circle.Chinese and western medicine is all constantly being strengthened incidence of coronary heart disease mechanism and the research of clinical treatment.At present, the common method for the treatment of of coronary heart disease includes Drug therapy and myocardial revascularization treatment, and myocardial revascularization treatment includes interventional therapy and surgery coronary artery bypass grafting.Drug therapy is the basis of all treatments, Drug therapy has western medical treatment and Chinese traditional treatment, western medicine is based on thrombolytic of infusing, research proves, long-term infusion is the biggest to the negative effect of blood vessel and heart, the traditional Chinese medical science takes the means that Qi-benefiting and heart-nourishing, promoting blood circulation to remove obstruction in the collateral, damp eliminating are reduced phlegm, treatment coronary heart disease to have treating both the principal and secondary aspects of a disease effect, gradually approved by extensive patients and medical profession.
Summary of the invention
It is an object of the invention to provide a kind of medicine treating arteria coronaria Microvessel Dysfunction and preparation method thereof, for coronary heart disease, myocardial ischemia, stable angina pectoris, myocardial infarction reconvalescent's blood circulation promoting and blood stasis dispelling, vigorate qi and replenish the blood.
The present invention is achieved in that a kind of medicine treating arteria coronaria Microvessel Dysfunction, the medicine of described treatment arteria coronaria Microvessel Dysfunction include Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, Radix Notoginseng powder 6g.
Another object of the present invention is to provide the preparation method of the medicine of a kind of described treatment arteria coronaria Microvessel Dysfunction, described preparation method comprises the following steps:
Weigh Chinese crude drug according to Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, add 11 times amount water, decoct 2 times, leaching medicinal liquid 300mL；
The Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong and Radix Ginseng are decocted into after medicinal liquid, Radix Notoginseng powder 6g is blended into.
Further, the medicine of the treatment arteria coronaria Microvessel Dysfunction that prepared by described preparation method each takes 150mL, every day 2 times.
The Yiqi Huoxue Recipe that the present invention provides can make MVC substantially increase, and illustrates that Yiqi Huoxue Recipe substantially increases Angiogenesis.Raising angiogenesis of pericyte is requisite.In angiogenesis, the endotheliocyte passage being newly formed needs the support raising pericyte or smooth muscle cell to give blood vessel physics and chemical.Heart infarction rat uses Yiqi Huoxue Recipe for Treatment, can count by reducing pericapillary cells, maintain the relative fullness of blood vessel, improve the blood flow of local microcirculation, reduce infarct size, and promote angiogenesis, thus reach to improve the effect of local myocardial blood supply.
Cardiac function can be effectively improved after Yiqi Huoxue Recipe for Treatment, increase the ejection fraction of heart, reduce myocardial infarction region, improve myocardial ischemia symptom.Benefiting QI for activating blood circulation can suppress acute myocardial infarction (AMI) rat relaxing period left ventricular interior diameter (LVDd) and systole left ventricular interior diameter (LVDs), especially notable to improve LVDs, thus improve AMI rat left chamber ejection fraction (EF), cardiac function enhancing.The clear and definite Yiqi Huoxue Recipe of result of study definite drug effect in terms of myocardial contraction and cardiac function, and long-term prescription effect is more notable.
Apply benefiting QI for activating blood circulation can increase the secretion of the vascular relaxing factors such as NO, PGI2 after cardiac infarction, reduce the vasoconstrictive factors such as ET-1, TXA2 horizontally through the balance between regulation vasoconstriction and diastole active substance, improve vasospasm, increase blood supply of cardiac muscle, repair damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue, the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus effectively improves Myocardial Microcirculation；Apply Yiqi Huoxue Recipe can reduce sTM, sEPCR level after myocardial infarction, by repairing damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue, the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus effectively improves Myocardial Microcirculation.
Benefiting QI for activating blood circulation can significantly reduce HWI, thus reduces myocardial hypertrophy, improves remodeling ventricle；Drugs for nourishing qi and activating blood effectively suppresses the expression of MMP-2 in cardiac muscular tissue in transcription and translation level, and Masson coloration result also proves that drugs for nourishing qi and activating blood can suppress myocardial fibrosis, the generation of suppression remodeling ventricle；Drugs for nourishing qi and activating blood can also be produced anti-fibrosis effect, and then improve EF by suppression TGF-β 1, improved remodeling ventricle.
Yiqi Huoxue Recipe improves heart infarction rat Coronary Microcirculation Function obstacle determined curative effect, drugs for nourishing qi and activating blood can reduce pericapillary cells counting, maintain the relative fullness of blood vessel, improve the blood flow of local microcirculation, reduce infarct size, and increase capillary density promotion angiogenesis, thus reach to improve the effect of local myocardial blood supply；Vascular endothelial function is protected from genes protein level; balance between regulation endogenous vasoconstrictors and diastole active substance; improve vasospasm; increase blood supply of cardiac muscle; repair damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue; the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus is effectively improved cardiac muscle arteria coronaria Microvessel Dysfunction
Accompanying drawing explanation
Fig. 1 is the process for preparing medicine flow chart of the treatment arteria coronaria Microvessel Dysfunction that the embodiment of the present invention provides.
Detailed description of the invention
For the summary of the invention of the present invention, feature and effect can be further appreciated that, hereby enumerate following example, and it is as follows to coordinate accompanying drawing to describe in detail.
The present invention is achieved in that a kind of medicine treating arteria coronaria Microvessel Dysfunction includes Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, Radix Notoginseng powder 6g.
As it is shown in figure 1, the process for preparing medicine of the treatment arteria coronaria Microvessel Dysfunction of the embodiment of the present invention comprises the following steps:
S101: weigh Chinese crude drug according to Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, adds 11 times amount water, decocts 2 times, leaching medicinal liquid about 300mL；
S102: decoct into after medicinal liquid by the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong and Radix Ginseng, is blended into Radix Notoginseng powder 6g.
The medicine of the treatment arteria coronaria Microvessel Dysfunction of the embodiment of the present invention each takes 150mL, every day 2 times.
Below in conjunction with experiment, the application effect of the present invention is explained in detail.
Test the Yiqi Huoxue Recipe research on the change impact of arteria coronaria Microvascular architecture 26S Proteasome Structure and Function
Medicine for treatment:
Yiqi Huoxue Recipe is made up of Radix Astragali, Radix Ginseng, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Notoginseng powder.Prepare according to oral agents technique, weigh Chinese crude drug in prescription ratio, add 9 times amount water, decoct 2 times, each 2.5 hours, totally 5 hours, decocting liquid filtered, and concentrated, and adds ethanol and adjusts alcohol content to 50%, filter, reclaim ethanol, filter, adjust concentration (the most every 1 milliliter is equivalent to crude drug amount 2 grams).
Animal Anesthesia and air flue are set up
Ramus descendens anterior arteriae coronariae sinistrae ligation is used to build animal model of acute myocardial infarction.Pentobarbital sodium (40mg/kg) intraperitoneal injection of anesthesia after rat weight, with 1%.Back fixation, in Mus plate, above plays left breast the second rib, down to the 5th rib, with breastbone for boundary's unhairing preserved skin.Mus plate is placed on 45 ° of operating-tables tilted (rat is head-up), light source irradiates Mus cervical region, with bundle by Mus tongue, upwards lift as far as possible, expose glottis, i.e. it may be clearly seen that the glottis of rat is opened and Guan Bi along with breathing, take advantage of animal air-breathing moment and rapidly tracheal intubation is inserted air flue, exiting tube core, be positioned over the mouth of pipe with staple, whether inspection intubates at air flue.Use immobilization with adhesive tape tracheal intubation, prepare respirator, adjust ventilation, 85 times/min of frequency, tidal volume 0.7-0.8ml, inspiratory/expiratory 1: 2, fraction of inspired oxygen 1.0, end expiratory positive pressure 2cmH2O.
Modeling 120 altogether, survives 89, and operation survival rate is 74.17%.By random digits table, modeling success rat is divided into following eight groups: 7 days groups of model (MI), 7 days groups of benefiting QI for activating blood circulation (Yiqihuoxue), 7 days groups of perindopril (Perindopril), 7 days groups of Tongxinluo (Tongxinluo), 28 days groups of model (MI), 28 days groups of benefiting QI for activating blood circulation (Yiqihuoxue), 28 days groups of perindopril (Perindopril), 28 days groups of Tongxinluo (Tongxinluo), plus sham-operation (Sham) 7 days groups, 28 days groups of sham-operation, totally ten groups.With row Electrocardioscopy in the 5th day after modeling, the amount of the Q ripple that statistics I, avL, V1-V6 lead total, it is judged that the order of severity of heart infarction, reject the rat that infarction degree is the heaviest or the lightest, finally including observation animal number in is 76.
Experimental result
(1) electrocardiogram
Ligation ramus descendens anterior arteriae coronariae sinistrae builds myocardial infarction model, the pathologic Q wave number amount screening model of appearance of leading according to 5 days after operation electrocardiogram I, aVL, V1-V6, and sees pathologic Q ripple sustainable existence when within the 28th day, drawing materials.
(2) cardiac ultrasonic result
Left ventricular interior diameter changes:
After heart infarction 7 days, compare with sham operated rats, model group relaxing period left ventricular interior diameter (LVDd) change is not notable (P>0.05), model group systole left ventricular interior diameter (LVDs) increases, difference statistically significant (P<0.05), compared with model group, administration group LVDs has reduction trend；After heart infarction 28 days, model group LVDd, LVDs dramatically increase (P < 0.05) than sham operated rats, administration group LVDd, LVDs have reduction trend, benefiting QI for activating blood circulation group, Tongxinluo group compare LVDs and reduce (P < 0.05) with model group, benefiting QI for activating blood circulation group LVDs reduces 10.4%, Tongxinluo group reduces 11.5%, and perindopril group reduces 7.9%.
Left ventricular function changes:
After heart infarction 7 days, comparing with sham operated rats, model group Left Ventricular Ejection Fraction (EF), left room short axial ratio (FS) are substantially reduced (P < 0.05), and compared with model group, administration group EF has increase trend；After heart infarction 28 days, model group EF, FS reduce (P < 0.05) than sham operated rats, administration group compares with model group, EF, FS have increase trend, benefiting QI for activating blood circulation group, Tongxinluo group EF increase notable (P < 0.05), Tongxinluo group adds 21%, and Tongxinluo group adds 2.5%, and perindopril group adds 16.7%.
Cardiac muscular tissue's observed result
Perusal
Sham operated rats heart size is moderate, and cardiac muscular tissue's form is normal, and color is scarlet, smooth surface.Model group heart size increases, and substantially subsides seen from left room, and left locular wall infarct location is thinning, and color is greyish white.Benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group heart size relatively sham operated rats significantly increase.Within 7 days, model group infarction size is less compared with 28 days model group, infarction lesser extent.Blood capillary is observed by CD34 antibody staining, and light Microscopic observation respectively organizes blood capillary situation, and blood capillary proliferation seen from sham operated rats is inconspicuous；A small amount of blood capillary proliferation seen from model group；The blood capillary of more hypertrophy seen from benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group.
Pathological staining result
Shown by after 10 × 40 times of light Microscopic observation myocardial infarctions 7 days and 28 days heart HE pathological staining results:
After infarction 7 days:
Sham operated rats myocardial cell queueing discipline, clear in structure, the accidental a small amount of inflammatory cell of iuntercellular；Model group infarcted region locular wall is thinning, and number of myocardial cells substantially reduces, myocardial cell arrangement disorder, massive inflammatory cells infiltrated；Infarct border district visible hyperemia and inflammatory cell band；Benefiting QI for activating blood circulation group rat myocardial cell structure disturbance, partial necrosis, inflammatory cell band seen from infarct border district；Tongxinluo group myocardial cell arrangement disorder, number of myocardial cells reduces, it is seen that inflammatory cell invades profit；Perindopril group myocardial cell arrangement disorder, it is seen that inflammatory cell invades profit.
After infarction 28 days:
Sham operated rats cell arrangement is neat, myocardial cell profit dish clear in structure；Model group infarcted region is the most thinning, fibrocyte and collagenous fiber bundle replace, infarct border district myocardial cell arrangement disorder, and inflammatory cell infiltration reduces；Benefiting QI for activating blood circulation group infarct border district rat myocardial cell structure disturbance, part inflammatory cell；Tongxinluo group rat myocardial cell arrangement disorder, myocardial cell reduces；Perindopril group rat myocardial cell arrangement disorder, myocardial cell reduces.
Masson coloration result
Masson dyeing RED sector is normal cardiac muscular tissue, and green portion is collagenous tissue, by 10 × 1.25 times, and 10 × 4 times, 10 × 40 times of observation by light microscope, can determine whether degree of myocardial fibrosis.
After infarction 7 days:
Rats in sham-operated group cardiac muscular tissue is normal, and only hanging wire site has a small amount of collagen fiber to be distributed；Model group infarcted region endocardium is that dispersivity is distributed to adventitia by collagen fiber；Benefiting QI for activating blood circulation group infarcted region endocardium to adventitia collagenous tissue is dispersivity distribution, and collagen fiber distribution is little compared with model group；The collagen dispersivity distribution of Tongxinluo group infarct border district, collagen content relatively model group reduces；Western medicine group collagen Dispersed precipitate is in cardiac muscular tissue, and collagen content relatively model group reduces.
More after death 28 days:
Rats in sham-operated group cardiac muscular tissue is normal, has no that obvious collagen fiber are distributed；Model group infarcted region endocardium is replaced to adventitia by collagenous tissue, and locular wall is thinning, and collagen fiber are dispersivity distribution；Benefiting QI for activating blood circulation group infarcted region collagen fiber are that dendron sample is distributed between cardiac muscular tissue distribution, and collagen fiber distribution is little compared with model group；Tongxinluo group infarcted region is replaced by collagen fiber, and infarct border district collagen fiber are wellability distribution, and collagen content relatively model group reduces；Western medicine group collagen Dispersed precipitate is in cardiac muscular tissue, and collagen content is less than model group.
Each group rat heart muscle non-infarcted region Microvessel Count (MVC) result
Heart infarction 7 days, after 28 days, comparing with sham operated rats, model group MVC substantially increases (P < 0.01), is administered after intervening, comparing with model group, benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group rat heart muscle non-infarcted region MVC express substantially increases (P < 0.05).
Test two Yiqi Huoxue Recipes to heart infarction rat model infarct border district MCD and the impact of pericyte
Drugs for nourishing qi and activating blood is mainly formed i.e. Radix Ginseng, Radix Astragali, Rhizoma Chuanxiong, Radix Angelicae Sinensis, Radix Notoginseng powder by five kinds of Chinese medicine.The drugs for nourishing qi and activating blood being used in this experiment observing is in early stage numerous studies, and the curative effect optimal dose that (from resistance and supplementing qi medicine, blood circulation promoting medicine, drugs for nourishing qi and activating blood (1:1), drugs for nourishing qi and activating blood (1:2), drugs for nourishing qi and activating blood (2:1)) is chosen in QI invigorating with the numerous proportioning of blood circulation promoting medicine combines (dosage combination that i.e. drugs for nourishing qi and activating blood (2:1) is organized).Medicine is provided by Pharmaceutical Factory of Beijing University of Chinese Medicine, processing technology is prepared according to oral agents technique, weigh up Chinese medicine according to side's medicine proportion of composing, add the water of 9 times amount, respectively decoct 2 times, totally 5 hours, time is identical every time, by medical filtration reconcentration, adds after ethanol is transferred to 50% alcohol content and again filters, then filtering after reclaiming ethanol, adjustment concentration is 1:2 (every 1 milliliter of suitable crude drug amount 2 grams).
Choose male SD rat, body weight 220 scholar 20g, 100.It is randomly divided into modeling group and sham operated rats.Model group rats uses the method for ramus descendens anterior arteriae coronariae sinistrae ligation.After 1% pentobarbital sodium lumbar injection (40mg/kg) general anesthesia, rat is lain on the back and is fixed on surgical plate, incidence is naturally stretched and fixes, operative region preserved skin is sterilized, Mus plate is placed on 45 ° of operating-tables tilted, Mus cervical region is irradiated with cold light source, Mus tongue is upwards lifted, it may be clearly seen that the glottis of rat is along with breathing folding, take advantage of animal air-breathing moment and rapidly tracheal intubation is inserted air flue, exit tube core, cotton thread is positioned over the mouth of pipe, the air-flow that staple passes in and out along with the mouth of pipe swings, whether i.e. susceptible of proof intubates at air flue, by Dispoable medical immobilization with adhesive tape tracheal intubation after confirming in air flue.Select the preoperative respiratory frequency of rat at 70～100 times/min, connect toy respirator, adjust ventilation, inspiratory/expiratory 1:2,85 times/min of respiratory frequency, tidal volume 0.70.8ml, fraction of inspired oxygen 1.0, end expiratory positive pressure 2cmH2O, then open respirator.ANER DIAN range of operation is sterilized again; paving operation towel; third and fourth intercostal incision skin in left side; blunt separation muscle layer; open thoracic cavity; left lung is oppressed downwards to protect lungs with aseptic wet cotton balls; with be parallel to intercostal direction place ophthalmology eye speculum push open thymus expand the visual field; tearing pericardium gently with curved tweezer makes heart fully expose; major part animal can see that between left auricle lower edge and pulmonary conus great cardiac vein trunk traveling and branch thereof, left anterior descending coronary artery (LAD) accompany row therewith.Left auricle is pushed gently aside with aseptic cotton carrier, 5-0 swaged needle is clamped at left auricle lower edge about 2mm with needle holder, along anterior descending branch initial part inserting needle, left anterior descending branch is ligatured together with a small amount of cardiac muscular tissue, depth of needle 0.5mm, width 2～3mm, then rapidly heart is resetted, taking out remaining apparatus etc. of the residuals such as intrathoracic cotton balls, thoroughly layer-by-layer suture rib, muscle and skin after hemostasis, close thoracic cavity.Then respirator is removed.
The successful mark of modeling is that below ligation position cardiac muscle is graying in vain, beats and weaken, and monitor ECG limb is derived the existing ST section back of a bow and the most substantially raised.Immediate postoperative gives preventive usage: 0.2ml lignocaine lumbar injection, 0.2ml furosemide lumbar injection, to reduce incidence of arrhythmia and to alleviate heart volume load.Because being to have invasive procedures, in order to prevent to infect postoperative intramuscular injection penicillin for three days on end.All operation process completes in 30min, strict aseptic technique.The electrocardiogram sham operated rats operation process of record respectively preoperative, postoperative is identical, only walks around left coronary artery, beats untwisting.Model group and the postoperative conventional raising of sham operated rats animal.
Successful for modeling rat is carried out random packet, respectively: model group, Chinese drug-treated group, perindopril group, Tongxinluo group, sham operated rats as a control group, 5 groups altogether.Each group started gavage relative medicine, every day 1 time respectively in postoperative 1st day.The selection of drug dose: drugs for nourishing qi and activating blood group (21g/kg body weight d, early-stage Study is established), perindopril group (0.72mg/kg body weight d, clinical equivalent dosage, according to seeing As-Is analysis and document), Tongxinluo group (30mg/kg body weight d).These three medicine is dissolved in sterile distilled water respectively, the concentration adjusting each medicine makes every animal reach the medication volume of 10mL/ (kg d), and also should ensure that drug dose needed for every day, sham operated rats and model group are without medicine, but still need to every day with 10mL/ (kg d) sterile distilled water gavage.
After the medicine that each group intervenes use above is dissolved in sterile distilled water, adjusting concentration and make each group to reach medication volume 1ml/100g/d, carry out gavage, primary premise is to ensure that drug dose.
Result
Myocardial infarction marginal zone capillary density
Each group of rat myocardial infarction model marginal zone mean vascular surface density (MCD) is measured under Pathologic image analysis system.7th day:
Model group relatively sham operated rats myocardial infarction marginal zone MCD substantially reduces (P < 0.01), Yiqi Huoxue TCM group, perindopril group, Tongxinluo group relatively model group compare, the equal showed increased of MVD (P < 0.01) of its myocardial infarction marginal zone, Yiqi Huoxue TCM group MCD increases the most notable, compared with perindopril group, Tongxinluo group statistically significant (P < 0.01).28th day: model group relatively sham operated rats myocardial infarction marginal zone MCD substantially reduces (P < 0.01), Yiqi Huoxue TCM group, perindopril group, Tongxinluo group relatively model group compare, the equal showed increased of MCD (P < 0.01) of its myocardial infarction marginal zone, Western medicine group MCD increases the most notable, compared with benefiting QI for activating blood circulation group, Tongxinluo group statistically significant (P < 0.01).In addition to sham operated rats, each group rat the 7th day is higher than 28 days capillary densities.
Pericapillary cells counts
7th day, model group relatively pericyte of sham operated rats infarct border district counting substantially increases, Yiqi Huoxue TCM group, perindopril group, Tongxinluo group are compared with model group, pericyte's counting in infarct border district reduces (P < 0.01), and wherein benefiting QI for activating blood circulation group relatively perindopril group and Tongxinluo group have notable difference (P < 0.01).28th day, model group relatively pericyte of sham operated rats infarct border district counting substantially increases, Yiqi Huoxue TCM group, perindopril group, Tongxinluo group are compared with model group, pericyte's counting in infarct border district significantly reduces (P < 0.01), and wherein perindopril group relatively benefiting QI for activating blood circulation group and Tongxinluo group have notable difference (P < 0.05 or P < 0.01).
Test the impact on heart infarction rat model serum NO level/ET-1, PGI2/TXA2 of three Yiqi Huoxue Recipes
Laboratory animal is with experiment two, and Experimental agents, with experiment two, is grouped and is administered with experiment two.
Using double antibody sandwich ELISA to measure serum NO level, the change of ET-1, PGI2, TXA2, concrete grammar strictly press test kit explanation and is operated, according to each group of rat in experimentation survive quantity observe 7 respectively, the situation of change of two time point indexs of 28d.
Result
Serum ET-1, NO level and PGI2, TXA2 level
Model group compares with sham operated rats, and model group rats Serum ET-1, TXA2 content are significantly raised, and NO, PGI2 level declines, and has significant differences (P < 0.01).Comparing with model group, benefiting QI for activating blood circulation group, perindopril group and Tongxinluo group ET-1, TXA2 content decline, and NO, PGI2 level is significantly raised, has significant difference (P < 0.05 or P < 0.01).Along with the increase of administration time, medicine effect strengthens, and the effect of perindopril is better than benefiting QI for activating blood circulation group and Tongxinluo group, after no significant difference between the two.
Test four drugs for nourishing qi and activating blood to heart infarction rat model infarct border district TM, EPCRmRNA and the impact of protein expression
Animal is with experiment two, and Experimental agents, with experiment two, is grouped and is administered with experiment two.
Result
Model group compares with sham operated rats, and in model group rats cardiac muscular tissue, the mRNA content of EPCR, TM is significantly raised, has significant difference (P < 0.01).Comparing with model group, benefiting QI for activating blood circulation group, perindopril group and Tongxinluo group EPCR, the mRNA content of TM decline, and have significant difference (P < 0.01).Wherein the effect of perindopril is better than benefiting QI for activating blood circulation group and Tongxinluo group, after no significant difference between the two.
The protein expression of cardiac muscular tissue EPCR, TM
Postoperative 7 days: model group compares with sham operated rats, in model group rats cardiac muscular tissue, the protein expression of EPCR, TM was decreased obviously, and had significant difference (P < 0.01).Comparing with model group, benefiting QI for activating blood circulation group, perindopril group and Tongxinluo group EPCR, the protein expression of TM raise, and have significant difference (P < 0.01 or P < 0.05).Wherein the effect of benefiting QI for activating blood circulation group is better than perindopril and Tongxinluo group, after no significant difference between the two.Postoperative 28 days: model group compares with sham operated rats, in model group rats cardiac muscular tissue, the protein expression of EPCR, TM was decreased obviously, and had significant difference (P < 0.01).Comparing with model group, benefiting QI for activating blood circulation group, perindopril group and Tongxinluo group EPCR, the protein expression of TM raise, and have significant difference (P < 0.01 or P < 0.05).Wherein the effect of benefiting QI for activating blood circulation group and Tongxinluo group is better than perindopril, nothing between the above two.
Test the impact on heart infarction rat model serum sTM, sEPCR of five Yiqi Huoxue TCMs
Animal, with experiment two, is grouped and is administered with experiment two.
The horizontal model group of serum EPCR, TM compares with sham operated rats, and model group rats serum EPCR, TM content is significantly raised, has significant difference
(P<0.01).Comparing with model group, benefiting QI for activating blood circulation group, perindopril group and Tongxinluo group EPCR, TM content decline, and have significant difference (P < 0.01).Wherein, 7 days time points, benefiting QI for activating blood circulation group effect is better than Tongxinluo group and perindopril group；
28 days time points, the effect of perindopril is better than benefiting QI for activating blood circulation group and Tongxinluo group, after no significant difference between the two.
Test the formation of six heart infarction ventricular remodeling in rats and Yiqi Huoxue TCM to its influence research
Animal, packet, medication are with experiment one
Experimental result
Cardiac index (HWI)
After result display heart infarction, 7 days model group relatively sham operated rats HWI substantially increase (P < 0.05), administration group and model group
Relatively, rat HWI has downward trend, but each group difference is not notable (P > 0.05)；After heart infarction after 28 days, with vacation
Operation group is compared, and model group rats HWI substantially rises, difference statistically significant (P < 0.05), is administered after intervening, benefit
Invigorate blood circulation group, Tongxinluo group, the HWI of perindopril group rat of gas is decreased obviously (P < 0.05), and benefiting QI for activating blood circulation group have dropped
11.4%, Tongxinluo group have dropped 14.3%, and perindopril group have dropped 11.4%.
Each group rat heart muscle MMP2mRNA expression of results
After heart infarction 7 days, model group compares MMP2mRNA and expresses substantially increase (P < 0.01) with sham operated rats, is administered dry
Prognosis, benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group rat heart muscle MMP2mRNA express decline, and difference has statistics
Learn meaning (P < 0.05)；After heart infarction 28 days, model group MMP2mRNA expresses relatively sham operated rats increases (P < 0.01),
Administration group has downward trend.
Each group rat heart muscle MMP2 protein expression result
After heart infarction 7 days, comparing with sham operated rats, model group MMP2 albumen substantially increases (P < 0.01), is administered after intervening, and benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group rat heart muscle MMP2 protein expression are decreased obviously (P < 0.05)；After heart infarction 28 days, model group MMP2 protein expression relatively sham operated rats increases (P < 0.01), and administration group is decreased obviously trend.
Test seven drugs for nourishing qi and activating blood to the impact of rat TGF-β signal path after heart infarction
Laboratory animal, packet and medication are with experiment one
Experimental result
Cardiac muscular tissue's TGF-β 1mRNA expression of results
After heart infarction 7 days, model group is expressed on the rise compared with sham operated rats TGF-β 1mRNA, difference statistically significant (P < 0.05), is administered after intervening, compared with model group, each medicine group TGF-β 1 gene expression has downward trend (P < 0.05)；After heart infarction 28 days, comparing with sham operated rats, (P < 0.05) is increased in model group table TGF β-1 gene expression, compares with model group, and administration group TGF-β 1 gene expression declines (P < 0.05).
Cardiac muscular tissue's TGF-β 1 protein expression result
Result shows that 7 days model group relatively sham operated rats TGF-β 1 protein expressions increase, difference statistically significant (P < 0.05)；
Being administered after intervening, compared with model group, each medicine histone is expressed downward trend (P < 0.05)；Within 28 days, model group is compared with sham operated rats, and TGF-β 1 protein expression of model group rats dramatically increases, difference statistically significant (P < 0.05)；
After giving pharmaceutical intervention, each histone is expressed downward trend (P < 0.05).
Rat heart muscle TGF-β 1 protein expression ImmunohistochemistryResults Results
Immunohistochemical staining, brown is positive reaction, by being distributed by 10 × 40 times of observation by light microscope TGF-β 1 protein expressions:
After heart infarction 7 days:
Rats in sham-operated group cardiac muscle is normal, has a small amount of dark brown granule to be distributed in hanging wire site myocardial cell slurry；Model group infarcted region endocardium, to lamellar brown TGF-β 1 positive reactions a large amount of seen from adventitia, is distributed in dispersivity；Benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group infarcted region endocardium are distributed to lamellar brown TGF-β 1 positive reaction seen from adventitia, and the distribution of the brown positive is little compared with model group scope.
After infarction 28 days:
Rats in sham-operated group cardiac muscular tissue is normal, it is seen that brown TGF-β 1 granule is uniformly distributed；Model group infarct border district is distributed to points a large amount of seen from adventitia, lamellar dark-brown TGF-β 1 by endocardium, lamellar brown TGF-β 1 positive reaction distribution seen from benefiting QI for activating blood circulation group, Tongxinluo group, perindopril group infarct border district, the distribution of the brown positive is little compared with model group scope.
Yiqi Huoxue Recipe can make MVC substantially increase, and illustrates that drugs for nourishing qi and activating blood substantially increases Angiogenesis.Raising angiogenesis of pericyte is requisite.In angiogenesis, the endotheliocyte passage being newly formed needs the support raising pericyte or smooth muscle cell to give blood vessel physics and chemical.Heart infarction rat uses Yiqi Huoxue TCM treatment, can count by reducing pericapillary cells, maintain the relative fullness of blood vessel, improve the blood flow of local microcirculation, reduce infarct size, and promote angiogenesis, thus reach to improve the effect of local myocardial blood supply.
Cardiac function can be effectively improved after Yiqi Huoxue Recipe for Treatment, increase the ejection fraction of heart, reduce myocardial infarction region, improve myocardial ischemia symptom.Benefiting QI for activating blood circulation can suppress acute myocardial infarction (AMI) rat relaxing period left ventricular interior diameter (LVDd) and systole left ventricular interior diameter (LVDs), especially notable to improve LVDs, thus improve AMI rat left chamber ejection fraction (EF), cardiac function enhancing.The clear and definite Yiqi Huoxue Recipe of result of study definite drug effect in terms of myocardial contraction and cardiac function, and long-term prescription effect is more notable.
Apply benefiting QI for activating blood circulation can increase the secretion of the vascular relaxing factors such as NO, PGI2 after cardiac infarction, reduce the vasoconstrictive factors such as ET-1, TXA2 horizontally through the balance between regulation vasoconstriction and diastole active substance, improve vasospasm, increase blood supply of cardiac muscle, repair damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue, the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus effectively improves Myocardial Microcirculation；Apply Yiqi Huoxue Recipe can reduce sTM, sEPCR level after myocardial infarction, by repairing damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue, the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus effectively improves Myocardial Microcirculation.
Benefiting QI for activating blood circulation can significantly reduce HWI, thus reduces myocardial hypertrophy, improves remodeling ventricle；Drugs for nourishing qi and activating blood effectively suppresses the expression of MMP-2 in cardiac muscular tissue in transcription and translation level, and Masson coloration result also proves that drugs for nourishing qi and activating blood can suppress myocardial fibrosis, the generation of suppression remodeling ventricle；Drugs for nourishing qi and activating blood can also be produced anti-fibrosis effect, and then improve EF by suppression TGF-β 1, improved remodeling ventricle.
Yiqi Huoxue Recipe improves heart infarction rat Coronary Microcirculation Function obstacle determined curative effect, drugs for nourishing qi and activating blood can reduce pericapillary cells counting, maintain the relative fullness of blood vessel, improve the blood flow of local microcirculation, reduce infarct size, and increase capillary density promotion angiogenesis, thus reach to improve the effect of local myocardial blood supply；Vascular endothelial function is protected from genes protein level; balance between regulation endogenous vasoconstrictors and diastole active substance; improve vasospasm; increase blood supply of cardiac muscle; repair damaged endothelial cells function, reverse cellular morphology that ischemia, anoxia cause, function, the change of metabolism, increase the blood perfusion amount of local myocardial tissue; the blood supply improving myocardial cell regulates microcirculatory blood perfusion, thus is effectively improved cardiac muscle arteria coronaria Microvessel Dysfunction.
The present invention can be used for coronary heart disease, myocardial ischemia, stable angina pectoris, myocardial infarction convalescent period, show that the present invention can effectively alleviate cardiac muscle oxidative damage through pharmacological research, alleviate myocardial inflammation, dilating coronary blood vessel, improve blood supply of cardiac muscle and blood distribution, strengthen myocardial contraction, improve microcirculation, strengthen cardiac muscle energy supply, reduce apoptosis of cardiac muscle, and effectively alleviate every symptom of above-mentioned disease, improve patients ' life quality, improve patient moving ability.
With compared with types of drug, all medicines of the present invention are harmonious, and treating both the principal and secondary aspects of a disease has the merit of Yiqi-Huoxue-Huayu dredging collateral, can blood circulation promoting and blood stasis dispelling, vigorate qi and replenish the blood.
The above is only to presently preferred embodiments of the present invention, not the present invention is made any pro forma restriction, every technical spirit according to the present invention, to any simple modification made for any of the above embodiments, equivalent variations and modification, belongs in the range of technical solution of the present invention.
Claims (3)
1. the medicine treating arteria coronaria Microvessel Dysfunction, it is characterised in that the medicine of described treatment arteria coronaria Microvessel Dysfunction includes Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, Radix Notoginseng powder 6g.
2. the preparation method of the medicine of a treatment arteria coronaria Microvessel Dysfunction as claimed in claim 1, it is characterised in that described preparation method comprises the following steps:
Weigh Chinese crude drug according to Radix Astragali 30g, Radix Angelicae Sinensis 15g, Rhizoma Chuanxiong 12g, Radix Ginseng 10g, add 11 times amount water, decoct 2 times, leaching medicinal liquid 300mL；
The Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong and Radix Ginseng are decocted into after medicinal liquid, Radix Notoginseng powder 6g is blended into.
3. preparation method as claimed in claim 2, it is characterised in that the medicine for the treatment of arteria coronaria Microvessel Dysfunction prepared by described preparation method each takes 150mL, every day 2 times.
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| CN113181296A (en) * | 2021-05-18 | 2021-07-30 | 谭凯军 | Ginseng and gastrodia elata beverage |
| CN115252720A (en) * | 2021-05-19 | 2022-11-01 | 中国中医科学院医学实验中心 | Preparation method and application of qi-tonifying, blood-activating and yin-nourishing medicinal composition for delaying myocardial cell aging |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111838482A (en) * | 2020-07-20 | 2020-10-30 | 安徽康之味生物科技有限公司 | Preparation process of long-acting anti-fatigue salt carbonated water |
| CN113181296A (en) * | 2021-05-18 | 2021-07-30 | 谭凯军 | Ginseng and gastrodia elata beverage |
| CN115252720A (en) * | 2021-05-19 | 2022-11-01 | 中国中医科学院医学实验中心 | Preparation method and application of qi-tonifying, blood-activating and yin-nourishing medicinal composition for delaying myocardial cell aging |
| CN115252720B (en) * | 2021-05-19 | 2024-03-12 | 中国中医科学院医学实验中心 | Preparation method and application of qi-tonifying, blood-activating and yin-nourishing pharmaceutical composition for delaying myocardial cell aging |
| CN116270823A (en) * | 2023-02-10 | 2023-06-23 | 陕西省人民医院 | Medicine for improving endothelial index of coronary microcirculation dysfunction and identification method thereof |
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