CN103800349A - Effects of medicagenic acid-3-O-beta-D-glucopyranoside in resisting atherosclerosis, adjusting blood lipid and resisting myocardial ischemia - Google Patents
Effects of medicagenic acid-3-O-beta-D-glucopyranoside in resisting atherosclerosis, adjusting blood lipid and resisting myocardial ischemia Download PDFInfo
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- CN103800349A CN103800349A CN201210437351.XA CN201210437351A CN103800349A CN 103800349 A CN103800349 A CN 103800349A CN 201210437351 A CN201210437351 A CN 201210437351A CN 103800349 A CN103800349 A CN 103800349A
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Abstract
The invention relates to the field of natural medicine, and particularly relates to medical applications of medicagenic acid-3-O-beta-D-glucopyranoside having effects in resisting atherosclerosis, adjusting blood lipid and resisting myocardial ischemia. Pharmacological tests show that medicagenic acid-3-O-beta-D-glucopyranoside has the application in treatment of cardiovascular diseases, and especially has the efficacies of resisting atherosclerosis, adjusting blood lipid and resisting myocardial ischemia.
Description
Technical field
The present invention relates to the medical usage of a medicagenic acid-3-O-β-D-Glucose glycosides, it has atherosclerosis, adjusts blood fat and function of resisting myocardial ischemia.
Background technology
Hyperlipidemia (hyperlipidemias) is a kind of systemic disease, refer in blood T-CHOL (TC) and/or triglyceride (TG) is too high or HDL-C (HDL-C) is too low, modern medicine is referred to as dyslipidemia.It is the important risk factor that the cardiovascular and cerebrovascular disease such as atherosclerosis (AS) and coronary heart disease (CHD) occurs.Reduce the progress that blood fat can delay AS, and then reduce incidence rate and the mortality rate of cardio-cerebrovascular diseases, reduce the generation of myocardial ischemic injury.
Atherosclerosis is one common in angiopathy, is characterized in getting involved arterial disease from inner membrance.Generally first have that lipid and compound saccharide gather, hemorrhage and thrombosis, proliferation of fibrous tissue and calcinosis, and have medial gradually change in quality and calcification; pathological changes is often involved large and medium-sized flesh elastic-type tremulous pulse (take aorta, coronary artery and cerebral arteries as main); because the lipid outward appearance of gathering at endarterium is yellow medicated porridge sample, be therefore called atherosclerosis.Be enough to obstructing arterial chamber once this disease develops into, the tissue that this tremulous pulse is supplied or organ are by ischemia or necrosis.Wherein causing that the Etiological that myocardial ischemic injury occurs is coronary atherosclerosis, so suppress the formation of atheromatous plaque, is the important means that control myocardial ischemic injury occurs.Along with living standards of the people improve and dietary habit change, this disease also becomes the one of the main reasons of China's patient death.
In sum, blood fat reducing and atherosclerosis have significant protective effect to myocardial ischemia.
Inventor finds in the research in early stage, be present in the medicagenic acid-3-O-β-D-Glucose glycoside compound in the plant such as alfalfa (Medicago sativa L.) and Radix seu Cortex Heteropanacis (Dolichos falcatus KalcatusKlein), English medicagenicacid-3-O-β-D-glucopyranoside by name, be called for short MG, structural formula I is as follows, has good atherosclerosis, adjusts blood fat and function of resisting myocardial ischemia.
Summary of the invention
The invention discloses the purposes that MG is used for the treatment of cardiovascular disease, the preferred hyperlipidemia of described cardiovascular disease, atherosclerosis and treating myocardial ischemia damage.Part pharmacological testing and the result of the present invention about MG below.
The specific embodiment
Below in conjunction with specific embodiment, the invention will be further described, can be implemented, but illustrated embodiment is not as a limitation of the invention so that those skilled in the art can better understand the present invention also.
Embodiment 1
The preparation of MG
Get Radix seu Cortex Heteropanacis granule 250g, be placed in the round-bottomed flask of 5L, add the ethanol of the volumetric concentration 60% of 10 times of weight of Radix seu Cortex Heteropanacis granule, soak after 2 hours, water-bath reflux, extract,, extracts three times altogether, and extraction time is respectively 2,1.5,1 hours, merging filtrate.Decompression filtrate recycling ethanol, to without after alcohol taste, is configured to the medicinal liquid containing 0.05g raw medicinal herbs/mL; It is 5 that medicinal liquid is adjusted PH with hydrochloric acid; By processed good HPD100 type macroporous adsorptive resins on the medicinal liquid preparing, the blade diameter length ratio of post is 1: 5, take medical material amount, as 3: 5, (amount of loading medicinal liquid limited with the weight of its corresponding Radix seu Cortex Heteropanacis granule applied sample amount with weight resin ratio, be from being 3: 5 Radix seu Cortex Heteropanacis granule obtains medicinal liquid with weight resin ratio), loading flow velocity is 1BV/h.After loading, with the concentration of 8 times of column volumes be 30% alcohol flushing remove impurity, flow velocity is 2.5BV/h, be 60% ethanol elution by the concentration of 6 times of column volumes again, flow velocity is 2BV/h, and collecting concentration is 60% eluent, concentrated, dry, obtain MG (HPLC method is measured purity >=90%).
Embodiment 2
Rabbit hyperlipidemia merges Atherosclerosis Model
1. tested medicine
Administration sample: self-control MG sample (HPLC method is measured purity >=90%); Control drug: simvastatin (produce by Suzhou Yu Shi Pharmaceutical; Lot number: H20065361).All samples is all prepared with 0.3% CMC-Na.
2. laboratory animal
30 of healthy male Japan large ear rabbits, purchased from Tongji Medical College, Huazhong Science and Technology Univ., rabbit 7-8 in age week, body weight 2.0 ± 0.2kg.Each group all single cage is raised, and 12h illumination/dark is controlled room temperature in 24 ± 1 ℃, and humidity 50-60%, ventilates, its anti-noise.
3. main agents and equipment
Feed ingredient: common rabbit feedstuff (Tongji Medical College, Huazhong Science and Technology Univ.'s Experimental Animal Center); High lipid food [14% yolk powder+5% Adeps Sus domestica+1% cholesterol (Shanghai Hui Shi biochemical reagents company limited, lot number: 110412)]
(Bioengineering Research Institute is built up in Nanjing to Triglyceride Reagent box, lot number: 20120516); (Bioengineering Research Institute is built up in Nanjing to T-CHOL test kit, lot number: 20120720); (Bioengineering Research Institute is built up in Nanjing to low-density LP determination reagent box, lot number: 20120520); TGL-20M refrigerated centrifuger (Hunan instrument centrifuge instrument company limited); LA204 electronic balance (Heng Qichang of Changshu City); 721 spectrophotometers (Shanghai the 3rd analytical tool factory).
4. experimental technique
4.1 groupings: be divided at random 5 groups by body weight, 6 every group.Be respectively blank group, model group, MG high dose group (20mg/kg), MG low dose group (10mg/kg) and simvastatin group (5mg/kg).
4.2 model preparations:
4.2.1 foreign protein injection: experiment starts slowly to be injected by auricular vein the same day, gives model group, high group of MG, low group of MG and simvastatin group rabbit bovine serum albumin 1g/kg.
4.2.2 forage feed: blank group gives normal diet 2 times every day; Other adds normal diet after organizing the high lipid food (120-150g/d) of feeding early morning every day again; Amount to 14 weeks.
4.3 medications: MG high dose group gavage gives the MG of 20mg/kg, MG low dose group gavage gives the MG of 10mg/kg, and simvastatin group gavage gives 5mg/kg simvastatin, and model group and blank group give the CMC-Na solution of equivalent volumes, amount to 14 weeks.
4.4 blood specimen collections and index of correlation are measured
4.4.1 acquisition time and method: in testing for the 14th weekend by rabbit fasting 8h, through rabbit ear edge intravenous injection 10% chloral hydrate (1ml/kg) anesthesia, gather whole blood by heart.
4.4.2 blood is preserved and is separated: after blood specimen collection, be stored in immediately in 0 ℃ of frozen water, 10min is interior with censorship immediately after the centrifugal 5min of 4000r/min.
4.4.3 testing index: the same alcohol of the total gallbladder of serum (TC), triglyceride (TG), HDL-C (HDL-C) and low-density lipoprotein cholesterol (LDL-C).
4.5 aorta sample collections and tonyred dyeing
4.5.1 draw materials: cut rabbit anesthesia tailing edge median line open rabbit thoracic cavity and abdominal cavity, after collection blood preparation, separate immediately from aortic root to bilateral common iliac artery crotch aorta, normal saline flushing aorta.
4.5.2 dyeing: adopt Sudan IV staining, result decision method faces up the tunica intima after dyeing, by glass plate (thick 2mm) pressing tunica intima, on glass plate, put a transparent membrane, mark tremulous pulse border and extent of disease, the figure on thin film is changed into picture file with scanner.Carry out quantitative analysis with Image software, systematic survey plaque area, the blood vessel gross area, calculate plaque area and account for the percent of the aortic tunica intima gross area.
4.6 statistical procedures:
Adopt statistic software SPSS 10.0 to test to each group of experimental data, each Sets of Measurement Data is with mean ± standard deviation
represent, between group relatively with one factor analysis of variance and t check, rate relatively use chi-square analysis.With P < 0.05 for thering is statistical significance.
5 experimental results and analysis
After rabbit modeling, more blank group of equal significance of percent that model group blood TC, TG, HDL-C, LDL-C and plaque area account for the aortic tunica intima gross area changes, and shows modeling success.Give after MG high and low dose and simvastatin, all can make modeling after abnormal physical signs return to gradually normal level scope, and the effect of MG high dose group is suitable with simvastatin drug effect, the results are shown in Table 1.
Table 1MG merges the improvement effect of tremulous pulse medicated porridge hardening model to rabbit hyperlipidemia
(n=6)
#p < 0.05,
##p < 0.01,
###p < 0.001, the blank group of vs.
*p < 0.05,
*p < 0.01,
* *p < 0.001, vs model group.
Embodiment 3
Model Rats with Acute Myocardial Ischemia
1. tested medicine
Administration sample: self-control MG sample (HPLC method is measured purity >=90%).
2. laboratory animal
Healthy Wistar rat, male, body weight 250～300g, purchased from Tongji Medical College, Huazhong Science and Technology Univ.'s experimental animal center, quality licence number: SCXK-(Hubei Province) 2007-2001.12h illumination/dark, controls room temperature in 24 ± 1 ℃, and humidity 50-60%, ventilates.
3. main agents and equipment
Urethane, triphenyltetrazolium chloride (Triphenyltetrazolium chlorid, TTC) (Shanghai reagent company of Chinese Medicine group), BL-420 biological function experimental system, dw-3000 toy artificial respirator (Shanghai Jing Gong Industrial Co., Ltd.).
4. experimental technique
4.1 groupings: male rat is divided into sham operated rats, model group, MG low dose group (20mg/kg), MG high dose group (40mg/kg), 15 every group at random by body weight.Sham operated rats and model group give normal saline, and 0.5ml/100g gavage is pressed in MG administration, in advance administration 10d.
4.2 model preparations:
Rat gives after 20% urethane intraperitoneal injection of anesthesia by 6ml/kg, fixing.The chaeta at cervical region center, left front breast, extremity place is cut, connected BL-420 biological function experimental system electrocardio wire, whole process records II lead electrocardiogram.In the positive split shed of cervical region, separate right carotid intubate, Bonding pressure transducer records arteriotony.The circulation of qi promoting cannula of going forward side by side.After opening breast, connect toy artificial respirator.Cut off pericardium, between pulmonary conus and left auricle, flat left auricle lower edge is found ramus descendens anterior arteriae coronariae sinistrae (LAD), and at its underpass.Wait breathing, blood pressure steadily after, ligature is passed in the middle of PE pipe (diameter 2mm), with PE pipe one end blocking-up coronary flow, the other end is fixed with bulldog clamp.After ischemia 30min, unclamp bulldog clamp, then pour into 120min.Ischemia is successfully masked as: II ST-segment, the broadening of R ripple, arteriotony decline 20%-30%.Perfusion is successfully masked as again: the ST section of raising declines more than 50%, and arteriotony raises.Sham operated rats is opened coronary artery underpass after breast, not ligation.
4.3 observation index
4.3.1 test whole process and record II lead electrocardiogram, observe in ischemia 30min and pour into again 120min during occurrence type, frequency and persistent period of ventricular arrhythmia.The premature ventricular beat number of times that counts respectively, quivers the persistent period in ventricular tachycardia persistent period and chamber.
4.3.2 the mensuration of myocardial infarct size
Except sham operated rats, 5 rats of all the other random taking-ups of each group, in pouring into again 2h end Banded Rats ramus descendens anterior arteriae coronariae sinistrae (LAD), 1% Azo-Blue liquid 3mL is injected and carries out the cardiac muscle dyeing of left chamber through right common carotid artery, distinguish ischemic region (Fei Lanran district) and non-ischemic region (Lan Ranqu).Put to death animal, take out rapidly heart, rinse with phosphate buffer (PBS, pH7.4), filter paper blots surface moisture, puts-20 ℃ of refrigerator and cooled but.
Cardiac muscle TTC dyeing :-20 ℃ of refrigerator and cooled are hidden 30min, cut off atrium and right ventricle after taking-up, by the centripetal basilar part direction of apex, heart are cut into 2mm slab.Myocardium sheet is immersed in 1%TTC phosphate buffer (pH7.4), hatch 20min for 37 ℃, to distinguish not infarcted region (brick-red) and infarcted region (canescence) of ischemia.
Fix, weigh, scan: take out after myocardium sheet filter paper blots and weigh.Its colorful digital is taken pictures, and image input computer is preserved.Myocardium sheet after scanning is kept at fixing 24h in 10% neutral formalin solution, to strengthen dyed color contrast, paraffin embedding subsequently.Area estimation, calculating.Process through above, blueness is dyed by Azo-Blue solution in non-ischemic region, and ischemia hazardous area comprises bolarious survival myocardium and the greyish white infarction tissue not being colored.According to three kinds of colors on myocardium sheet surface, measure respectively Infarct area and ischemic region area and account for the percentage ratio of full wafer cardiac muscle tangent plane with computerized image analysis software.The weight that area percentage is multiplied by this sheet cardiac muscle draws Gai Pian myocardial infarction district's weight and ischemia hazardous area weight.Respectively after Ge Pian myocardial infarction district's weight and ischemia hazardous area weight summation divided by whole cardiac weight, draw the ratio (IS/AAR) in myocardial infarction district (infarctsize, IS), ischemia hazardous area (AAR) and infarcted region with the ischemia hazardous area of whole heart.
4.4 statistical procedures:
Adopt statistic software SPSS 10.0 to test to each group of experimental data, each Sets of Measurement Data is with mean ± standard deviation
represent, between group relatively with one factor analysis of variance and t check, rate relatively use chi-square analysis.With P < 0.05 for thering is statistical significance.
5 experimental results and analysis
The impact of 5.1MG on blocking-up rat ramus descendens anterior arteriae coronariae sinistrae induction room arrhythmia
There is not malignant ventricular arrhythmia in sham operated rats, the whole generation chamber arrhythmias of model group illustrate modeling success.
Using ischemia 0-30min and during pouring into again 0-10min as the ARR examination phase.After myocardial ischemia 5min, start to occur arrhythmia, 10-15min arrhythmia is the most frequent and serious; Pour into again 0-5min arrhythmia comparatively common.
MG group premature ventricular beat obviously reduces, and has significance (P < 0.05) with model group comparing difference.The incidence rate of quivering in ventricular tachycardia (chamber speed) and chamber reduces, and the persistent period obviously shortens, and relatively has significant difference (P < 0.05) with model group.The results are shown in Table 2.
The impact of table 2MG on blocking-up rat ramus descendens anterior arteriae coronariae sinistrae induction room arrhythmia
(n=10)
*p < 0.05,
*p < 0.01, vs model group.
The impact of 5.2MG on Acute Myocardial Ischemia in Rats reperfusion injury myocardial infarction area
Table 3 is that sham operated rats, model group and MG high and low dose group cardiac muscle dangerous area (AAR) account for left ventricle area (LV) percentage ratio (AAR/LV%), infarcted myocardium (IS) accounts for the area percentage (IS/AAR%) of hazardous area cardiac muscle, and infarcted myocardium area accounts for the comparison of left chamber area percentage (IS/LV%).Known from result, AAR/LV percentage rate MG group more all has significant difference with model group.MG group IS/AAR% and IS/LV% are all lower than model group (P < 0.05 or P < 0.01).
The impact of table 3MG on myocardial ischemia reperfusion in rats infarct size
(n=10)
*p < 0.05,
*p < 0.01, vs model group.
Described in summary, medicagenic acid-3-O-β-D-Glucose glycosides (MG) can effectively regulate the blood fat of hyperlipidemia rabbit, suppresses the formation of atheromatous plaque.Meanwhile, it has alleviation protective effect to Acute Myocardial Ischemia in Rats.
Claims (4)
1. medicagenic acid-3-O-β-D-Glucose glycosides (structural formula I) is for the preparation of the medicinal usage of Cardiovarscular:
2. the purposes of medicine according to claim 1, wherein cardiovascular disease is hyperlipidemia.
3. the purposes of medicine according to claim 1, wherein cardiovascular disease is atherosclerosis.
4. the purposes of medicine according to claim 1, wherein cardiovascular disease is treating myocardial ischemia damage.
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| CN1850836A (en) * | 2006-05-23 | 2006-10-25 | 中国人民解放军第二军医大学 | Celosia argentea suponin compound and its pharmaceutical use |
| CN102379892A (en) * | 2011-10-08 | 2012-03-21 | 中国药科大学 | Blood lipid regulation, antiatherosclerotic and anti-myocardial ischemia functions of clematichinenoside |
| CN103494868A (en) * | 2013-09-27 | 2014-01-08 | 陈旅翼 | Application of total saponins of falcate dolichos root leaf in resisting atherosclerosis, regulating blood-lipid and resisting myocardial ischemia |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850836A (en) * | 2006-05-23 | 2006-10-25 | 中国人民解放军第二军医大学 | Celosia argentea suponin compound and its pharmaceutical use |
| CN102379892A (en) * | 2011-10-08 | 2012-03-21 | 中国药科大学 | Blood lipid regulation, antiatherosclerotic and anti-myocardial ischemia functions of clematichinenoside |
| CN103494868A (en) * | 2013-09-27 | 2014-01-08 | 陈旅翼 | Application of total saponins of falcate dolichos root leaf in resisting atherosclerosis, regulating blood-lipid and resisting myocardial ischemia |
Non-Patent Citations (1)
| Title |
|---|
| 邴飞虹等: "苜蓿总皂苷提取物抗动脉粥样硬化和降血脂的实验研究", 《时针国医国药》 * |
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