CN101306158B - Use of traditional Chinese medicine in preparing medicine for treating myocardial infarction - Google Patents
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Abstract
The invention discloses the application of a Chinese traditional medicinal combination in preparing the medicaments used for curing myocardial infarction. The Chinese traditional medicinal combination inhibits the activity of matrix metalloproteinase, the damage to the heart support structure, the progressive ventricular dilatation, and the change of gene phenotype of the heavy chain of myosin of the cardiac muscle during the reversion of the restructuring of the cardiac muscle, thus inhibiting the restructuring of the cardiac muscle after myocardial infarction, improving the function of heart after myocardial infarction so that sufferers of myocardial infarction benefit from the Chinese traditional medicinal combination clinically, or the prognoses of myocardial infarction is improved.
Description
Technical field
The present invention relates to a kind of new purposes of Chinese medicine composition, particularly, relate to the application of a kind of Chinese medicine composition in the medicine of preparation myocardial infarction.
Background technology
Myocardial infarction (MI) is a coronary occlusion, and blood flow interrupts, and makes the part cardiac muscle because of serious persistency ischemia local necrosis take place.Primary disease has 800,000 people that myocardial infarction takes place in American-European countries every year approximately, and 450,000 people's re-infarction, primary disease are in China and increase trend year by year.Because the cardiac muscle disappearance causes irreversible myocardial remodelling process, eventually to heart failure and death, healthy (the 10th edition 1237-1238 page or leaf in Chen Haozhu " practical internal medicine " People's Health Publisher July in 1997) of serious threat people.
Myocardial remodelling is that the basic pathology behind the myocardial infarction changes process, be influence MI closely, the one of the main reasons of long-term prognosis.Infarcted hearts experience myocardial remodelling process, promptly infarction position cicatrization, the remaining myocardial cell hypertrophy in non-infarction position, interstitial fibrosis and carrying out property ventricular chamber enlarge, and finally develop into heart failure.Numerous clinical trials confirm, and this process is carried out human intervention, delay its process, will bring huge income to MI patient.
Discover, the immunoinflammatory reaction participates in acute myocardial infarction (AMI) back myocardial remodelling, be important mechanisms (Liao Yuhua, Tao Rong, the Ching Cheong etc. of AMI postemphasis heart damage, myocardium inflammatory reaction and meaning thereof after the acute myocardial infarction, " Chinese molecule heart disease magazine ", 2002:2 (3): 7～9), different cytokine-expressing levels is the performance different efficacies in the development of this process with in lapsing to.Tumor necrosis factor (TNF-α) is a kind of proinflammatory cytokine, plays the acceleration myocardial necrosis in the development of AMI, worsens the effect of cardiac function.In early-stage Study, find, rat heart TNF-alpha expression is than sham operated rats significantly raise (Liu Ying, Liao Yuhua, Ching Cheong etc. behind the AMI, myocardium inflammatory reaction and cytokine-expressing [J] behind the rat myocardium block, " Chinese IMMUNOLOGY KEY WORDS INDEX, 2004:20 (12): 858-861).Anti-inflammatory factors cell IL-10 INTERLEUKIN-10 (IL-10) reached the peak in preceding 3 days behind the acute myocardial infarction, descend subsequently, rise out of proportion with other proinflammatory factors, thereby increase the weight of immune-mediated tissue injury (Deng Wei, Jiang Deqian, acute coronary incident patients serum's interleukin 10 and interleukin 12 level determination and clinical meaning [J], " Chinese circulation magazine ", 2000:15 (4): 236).
Matrix metalloproteinase (MMP) is the principal element of myocardial remodelling process mesostroma degraded behind the myocardial infarction, take place just to begin in back 1 day to activate at myocardial infarction, during reconstruct behind the myocardial infarction, matrix metalloproteinase 2 and 9 activity and express and all significantly increase.Suppress the activity of regional myocardial matrix metalloproteinase 2 after the infarction and 9, destroy and the ventricular dilatation of carrying out property, improve cardiac function thereby reduce behind the myocardial infarction matrix metal proteinase activity extracellular matrix degradation, the heart support structure that causes that raise.Myoglobulin heavy chain is also being brought into play important effect in the myocardial remodelling behind heart infarction.β myosin (β MHC) heavy chain embryonic gene takes place during myocardial remodelling express, albumen is synthetic in the myocyte duplicates with sarcomere to increase, and makes non-infarcted region cardiac muscle reactive plump; The α myosin (α MHC) that is expressed in the postnatal rat cardiac muscle then reduces.
The present invention is the improvement invention of carrying out on the basis of Chinese patent ZL02146573.8, quotes in full the content of this patent document record at this.Chinese patent ZL02146573.8 does not put down in writing the application of this Chinese medicine composition in the medicine of treatment myocardial infarction.The invention provides the new application of this Chinese medicine composition in the medicine of preparation treatment myocardial infarction.
Summary of the invention
The purpose of this invention is to provide the application of a kind of Chinese medicine composition in the medicine of preparation treatment myocardial infarction, it is characterized in that described Chinese medicine composition made by following bulk drugs:
Radix Astragali 150-450 part, Radix Aconiti Lateralis Preparata 40-120 part, Radix Ginseng or Radix Codonopsis 75-225 part, Radix Salviae Miltiorrhizae 75-225 part, Semen Lepidii (Semen Descurainiae) 50-150 part, Cortex Periplocae or CORTEX ACANTHOPANACIS 60-180 part, Rhizoma Alismatis 75-225 part, Rhizoma Polygonati Odorati 25-75 part, Ramulus Cinnamomi 30-90 part, Flos Carthami 30-90 part, Pericarpium Citri Reticulatae 25-75 part;
Preferably, described Chinese medicine composition is made by following bulk drugs:
450 parts of the Radixs Astragali, 112.5 parts of Radix Aconiti Lateralis Preparatas, Radix Ginseng or 225 parts of Radix Codonopsis, 225 parts of Radix Salviae Miltiorrhizaes, 150 parts of Semen Lepidii (Semen Descurainiae)s, Cortex Periplocae or 180 parts of CORTEX ACANTHOPANACIS, 225 parts of Rhizoma Alismatis, 75 parts of Rhizoma Polygonati Odorati, 90 parts of Ramulus Cinnamomi, 90 parts on Flos Carthami, 75 parts of Pericarpium Citri Reticulataes;
More preferably, the active component of described Chinese medicine composition is made up of the effective ingredient that the following step makes:
1) with the Radix Astragali, Semen Lepidii (Semen Descurainiae), Rhizoma Alismatis, Radix Ginseng or Radix Codonopsis, Cortex Periplocae or CORTEX ACANTHOPANACIS with an amount of 70% ethanol extraction, filter, concentrated extracting solution is the clear paste of 1.25-1.30 to relative density;
2) volatile oil of extraction Ramulus Cinnamomi, Pericarpium Citri Reticulatae;
3) add suitable quantity of water and decoct Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Polygonati Odorati, Flos Carthami, obtained aqueous solution is filtered; The aqueous solution that Ramulus Cinnamomi, Pericarpium Citri Reticulatae are carried behind the oil filters, and collects aqueous solution filtrate, adds suitable quantity of water again and decocts residue, filters, and merges aqueous solution; The various aqueous solutions of above-mentioned gained are merged, and being concentrated into relative density is the 1.25-1.30 clear paste, adds ethanol in the stirring, to determining alcohol 70%, leaves standstill, and filters, and it is the 1.25-1.30 clear paste that filtrate is concentrated into relative density.
Particularly, Chinese medicine composition of the present invention is by reducing the immunoregulation effect of myocardial cell proinflammatory cytokine and increase anti-inflammatory cytokines, the activity that suppresses regional myocardial matrix metalloproteinase 2 after the infarction and 9, reverse the change of myocardial myosin heavy chain gene phenotype in the myocardial remodelling process, suppress the MI myocardial remodelling, improve the MI cardiac function, thus the treatment myocardial infarction.
In the Chinese medicine composition of the present invention, as the latin name of the crude drug of active component and processing method thereof from " Chinese medicine voluminous dictionary " (in July, 1977, front page, Shanghai science tech publishing house) and " Chinese pharmacopoeia (version in 2005, Chemical Industry Press).
Chinese medicine composition of the present invention can also be routinely preparation process, for example, the preparation technology of Fan Biting " pharmacy of Chinese materia medica " (Shanghai Science Press 1997 December the 1st edition) record, make the acceptable any conventional dosage form of pharmaceutics, for example capsule, tablet, pill, oral liquid, soft capsule, drop pill etc.
In the application of the present invention, described Chinese medicine composition is a kind of in the preparations such as capsule, tablet, pill, oral liquid, soft capsule, drop pill, for above-mentioned dosage form can be realized, need when these dosage forms of preparation, to add the pharmacy acceptable auxiliary, for example: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, fixed, the Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods of acetic acid chloroethene; Substrate comprises: PEG6000, PEG4000, insect wax etc.For making above-mentioned dosage form can realize pharmacy of Chinese materia medica, need when these dosage forms of preparation, to add acceptable other adjuvant of pharmacy (adjuvant of each dosage form record among the Fan Biting " pharmacy of Chinese materia medica ", Shanghai Science Press December in 1997 the 1st edition).
One of purpose of the present invention provides above-mentioned Chinese medicine composition and improves application in the Heart Function After Myocardial Infarction medicine in preparation.
One of purpose of the present invention provides the application in the myocardial remodelling medicament after preparation suppresses myocardial infarction of above-mentioned Chinese medicine composition.
One of purpose of the present invention provides above-mentioned Chinese medicine composition and regulates myocardial cell proinflammatory cytokine and anti-inflammatory cytokines express application in the medicine behind the preparation myocardial infarction, reduce the expression of myocardial cell proinflammatory cytokine, increase anti-inflammatory cytokines and express, and reduce the ratio of myocardial cell proinflammatory cytokine and anti-inflammatory cytokines; Preferably, described proinflammatory cytokine is a tumor necrosis factor, and described anti-inflammatory cytokines is an IL-10 INTERLEUKIN-10.
One of purpose of the present invention provides above-mentioned Chinese medicine composition and suppress application in matrix metalloproteinase 2 and 9 active medicines behind the preparation myocardial infarction.
One of purpose of the present invention provides the application in above-mentioned Chinese medicine composition reverses myocardium myo globulin gene phenotype behind the preparation myocardial infarction the change medicine, increase the expression of α myosin, reduce the expression of β myosin, significantly rising α myosin and β myosin ratio improve myocardium contractile function on the whole.
The consumption of Chinese medicine composition of the present invention by active component crude drug gross weight, was 4-20 gram/days, but takes every day once, was preferably branch and took for 2-4 time, also was preferably 6-12 gram/day, divided and took for 2-4 time, more preferably 7.59 gram/days, divided and took for 3 times.
For illustrating the activity of traditional Chinese medicine composition for treating myocardial infarction of the present invention, use the capsule 's content dry powder (to call medicine of the present invention in the following text) that makes by embodiment 1 method to carry out following animal experiment.
1. materials and methods
1.1 the modeling grouping: healthy, male SD rat, body weight 180～250g is from Tongji Medical College, Huazhong Science and Technology Univ.'s animal center.Hydrochloric acid pentobarbital sodium 30mg/kg intraperitoneal injection anesthesia.The assisted respiartion of oral trachea cannula type toy respirator, tidal volume 2-3ml, inspiratory/expiratory 1:2, respiratory frequency 60 times/minute.Open breast through left front para T the 3rd, 4 intercostals, expose heart, cut off pericardium, make myocardial infarction model with 3-0 silk thread ligation left anterior descending branch (LAD) near-end, sew up the chambers of the heart at pulmonary conus and left auricle intersection.The postoperative survival person is divided into medicine of the present invention at random, and (Hebei Yi Ling medicine group provides, product batch number 060401) (MI-Q) group and infarction group (MI) are organized, be further divided into a week treatment subgroup (MI-Q1), all infarction subgroups (MI1), all around treat subgroup (MI--Q4) and around infarction subgroup (MI4), every group each 15.In addition with heart same area threading but the rat of the same race of not ligation anterior descending branch as sham-operation (S) group, all subgroups (S1) and around each 12 of subgroups (S4).
1.2 medication: MI-Q group is according to medicine of the present invention 50 times at the clinical patients consumption, and promptly 4g/kg/d is dissolved in the about 1.5ml of normal saline total amount, and in postoperative gastric infusion next day, MI group and S organize rat and give equivalent normal saline filling stomach at identical time point.
1.3 cardiac ultrasonic is estimated cardiac function:, use U.S. GE VIVID7 Ultrasound Instrument, frequency probe 10MHz respectively at 1 week and 4 weeks of postoperative.Fixing with lying on the back behind the rat anesthesia, obtain parasternal left side chamber major axis and papillary muscles horizontal stub shafts tangent plane.Detect index and comprise LVED (Left Ventricular End Systolic Dimension) (LVEDd), ejection fraction (EF) and shortening fraction (FS).
1.4 hemodynamics is measured: respectively at 1 week and 4 weeks of postoperative, behind the rat anesthesia, cut off skin of neck, isolate right carotid artery, the ligation distal end is clamped proximal part with bulldog clamp.Arterypuncture is inserted the 1mm polyethylene catheter, unclamps bulldog clamp, and conduit is slowly inserted left ventricle.Measure heart rate (HR) by tracing pressure transducer on the electrophysiological recording instrument synchronously, last pressure (LVSP), LVEDP (LVEDP) are shunk in left chamber, and calculate the maximum elevation rate of left ventricular pressure (± dp/dt).
1.5 cardiac muscular tissue's specimen is left and taken: inject 10% potassium chloride, 2～3ml through conduit, make asystole, open breast and cut heart, at the bottom of left chamber major axis midpoint is divided into heart in the apex of the heart half-sum heart perpendicular to major axis half in relaxing period.
1.6 histopathology: respectively at 1 week and 4 weeks of postoperative, 3 μ m are thick for paraffin embedding cardiac muscle specimen serial section, mounting microscopy after H-E dyeing.Cut into slices for every and under high power lens, get five visual field counting lymphocytes at random in infarcted region and non-infarcted region respectively, with the lymphocytic infiltration number of mean/high power lens as this section.
1.7 SABC detects cardiac bistiocyte's factor expression: respectively at 1 week and 4 weeks of postoperative, with myocardium specimen to be checked with the fixing 18h of 10% neutral buffered formalin.Dehydration, transparent, waxdip, paraffin embedding.3 μ m are thick for serial section, drag for sheet on the microscope slide that the poly-D-lysine anticreep was handled.Section dewaxes to water.3%H
2O
2Room temperature 10min deactivating endogenous peroxydase.Flushing back PBS soaks 5min.95 ℃ of microwave 10min repair antigen active.The sealing of 5% normal serum drips 1:200 dilution Mus IL-10 of the Chinese People's Anti-Japanese Military and Political College and TNF-Alpha antibodies respectively, 4 ℃ of overnight incubation.PH7.4 phosphate buffer (PBS) flushing 5min, 3 times.Drip biotinylation corresponding two anti-(Santa Cruz, Gary Fu Niya, the U.S.), hatch 20min for 37 ℃.PBS washes 5min, 3 times.Drip strepto-affinity element-biotin-peroxide multienzyme complex-horseradish peroxidase (SABC-HRP), hatch 20min for 37 ℃.PBS washes 5min, 3 times.Colour developing is to satisfaction, tap water cessation reaction under diaminobenzidine (DAB) room temperature.Haematoxylin is redyed nucleus 30s, the unnecessary dye liquor of flush away, and ethanol gradient dehydration back mounting, microscopically is observed.Under 10 * 40 times of light microscopics of multi-functional true color pathological image analysis system, 5 kens are selected in every section, and the unit are integral optical density (IOD/ area) of measuring the expression of each cytokine in each section carries out semi-quantitative analysis.
1.8 real-time quantitative RT-PCR detects cytokine-expressing: when 1 week of postoperative and 4 weeks, get each 100mg of infarcted region periphery cardiac muscle respectively and shred, use Trizol1000 μ l (U.S. MRC company) homogenate, extracting total tissue RNA.Use RT-PCR method reverse transcription to cDNA, the sequence that the equal reference gene of all primers storehouse (Genebank) provides, synthetic with Primer5.0, synthetic by Shanghai bio-engineering corporation.Design of primers is as follows: TNF-α (465bp): upstream: 5 '-CTG GGC AGC GTT TAT TCT-3 ', downstream: 5 '-TTGCTT CTT CCC TGT TCC-3 ', 54 ℃ of annealing temperatures; IL_10 (273bp): upstream: 5 '-AGTCAG CCA GAC CCA CAT-3 ', downstream: 5 '-GGC AAC CCA AGT AAC CCT-3 ', 56 ℃ of annealing temperatures; GAPDH (210bp): upstream: 5 '-GAT GGT GAA GGT CGG TGT G-3 ', downstream: 5 '-GAG GTC AAT GAA GGG GTC G-3 ', 60 ℃ of annealing temperatures.Reaction condition: use the reaction of SYBR Green I fluorescent dye technology row real-time quantitative PCR, according to follow procedure: circulate for the first time 94 ℃ 2 minutes, thereafter with 94 ℃ of degeneration 30 seconds; Annealed 30 seconds for 57 ℃, 72 ℃ were extended 30 seconds, circulated for 45 cycles last 72 ℃ of termination in 10 minutes.GAPDH is for referencial use with negative control, computer analysis Ct value, and the period that promptly fluorescence intensity reaches that system thinks in each reaction tube when having target DNA synthetic is in order to evaluate the real-time quantitative expression of each factor mRNA.
1.9 the activity of gelatin enzymatic assays cardiac muscular tissue metal matrix protease 2 and 9: postoperative is got infarction junctional area cardiac muscle during 4 weeks and is shredded, and extracts albumen with 50mmol/L Tris (Tris-HCl) homogenate.With Coomassie brilliant blue method (Bradford method) protein quantification.Behind protein extract and the sample loading buffer mixing, be splined on the 75g/L poly amic acid gel that contains the 2g/L gelatin, carry out sodium lauryl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis behind the adding label.Wherein whenever go up the sample hole and contain the 25g protein sample.Behind the about 1h of 50mA constant current electrophoresis, get glue, wash glue with 2.5% Triton X-100 (Triton-X-100) solution, in incubation reaction liquid, hatch 18h under 37 ℃, 0.5% Coomassie brilliant blue R, one 250 dyeing, destaining solution decolouring is till the negative staining band occurring clearly.(Britain UVP company) carries out graphical analysis with GSD8000 density scan analyser, enzymatic activity=band area * (band gray scale one background gray scale).
1.10 real time fluorescent quantitative inverse transcription polymerase chain reaction (PCR) detects α, β expression of myosin heavy chain mRNA: postoperative is got infarction junctional area cardiac muscle during 4 weeks and is shredded, with total RNA extraction reagent (Trizol) 1ml homogenate, extracting total tissue RNA, ultraviolet light test sample absorbance, A260/A280 are 1.8-2.0.Reverse transcription synthesizes cDNA.The reaction of SYBR Green I fluorescent dye method row real-time quantitative PCR.Design of primers is as follows:
α myosin heavy-chain mRNA: upstream 5 '-TATGCTGGCACCGTGGACTAC-3 ';
Downstream 5 '-GAGTTTGAGGGAGGACTTCTGG-3 '.
β myosin heavy-chain mRNA: upstream 5 '-CGACTTCAAAGGAGACCCAATC-3 ';
Downstream 5 '-CTATCACCTTCATGGCATCAGC-3 '.
GAPDH (confidential reference items): upstream 5 '-GATGGTGAAGGTCGGTGTG-3 ';
Downstream 5 '-GAGGTCAATGAAGGGGTCG-3 '.
Reaction condition: 94 ℃ of pre-degeneration 2min, again in 94 ℃ of degeneration 30sec, 57 ℃ of annealing 30sec, 72 ℃ are extended 30sec, repeat 45 circulations, extend 10min in 72 ℃ at last.Obtain the standard curve of respectively organizing specimen, carry software analysis Ct value by FTC2000 type real-time fluorescence quantitative PCR instrument (Shanghai Fengling Biological Technology Co. Ltd.).Calculate testing sample relative value.
1.11 statistical procedures: continuous data represents with x ± s, adopts SPSS10.0 software with processing such as t check, variance analysis and rectilinear correlation analyses.
2. result
2.1 Chinese medicine composition of the present invention is to the influence of MI rat cardiac function: compare with the S group, ultrasoundcardiogram shows that MI group rat left ventricle enlarges and contractile function reduces, and MI-Q group significantly minimizing left ventricle dilatation also improves ejection fraction.Hemodynamics result also shows: the maximum elevation rate of left ventricular pressure after the traditional Chinese medicine composition for treating of the present invention (± dp/dt) obviously enhancing (sees Table 1, Fig. 1).Two kinds of method testing results all show, with improving more remarkable effect than the cardiac function in 1 week of medication 4 weeks of traditional Chinese medicine composition for treating of the present invention.
Ultrasonic before and after table 1:MI 1 week of rat, the 4 weekends treatment, hemodynamics changes (x ± s)
Annotate: compare with sham operated rats (S group),
1)Expression P＜0.01,
2)Expression P＜0.05; Compare with the heart infarction group,
3)Expression P＜0.01,
4)Expression P＜0.05; LVEDd=left ventricular end diastolic dimension (mm); EF=ejection fraction (%); FS=shortening fraction (%); HR=heart rate (per minute heart beating number of times); LVSP=left ventricular systolic pressure (mmHg); LVEDP=left side chamber EDP (mmHg); The maximum climbing speed of+dp/dt=left ventricular pressure; The maximum fall off rate of-dp/dt=left ventricular pressure.
2.2 Chinese medicine composition of the present invention is to the influence of MI rat heart lymphocyte and myocardial cell factor expression: HE dyeing counting cardiac muscular tissue lymphocyte, the all visible a large amount of lymphocytic infiltrations of MI group infarcted region and non-infarcted region, obvious lymphocytic infiltration is not seen by S group cardiac muscular tissue, and the lymphocyte number that Drug therapy of the present invention is soaked into cardiac muscular tissue after to MI does not have obvious influence (on Fig. 2).Immunohistochemical staining shows that cardiac bistiocyte's factor mainly is expressed in the myocardial cell and non-infarcted region myocardial cell cytoplasm of infarcted region survival, and Chinese medicine composition of the present invention significantly reduces TNF-α protein expression and increases IL-10 protein expression (under Fig. 2).Compare with sham operated rats, MI group real-time quantitative RT-PCR detects the TNF-α of cardiac muscular tissue and IL-10mRNA and expresses significantly and increase, and TNF-alpha expression level raise during than 1 week during 4 weeks, and IL-10 was lower than for 1 week when expressing for 4 weeks slightly, and TNF-α/IL-10 ratio obviously raises.The MI-Q group traditional Chinese medicine composition for treating TNF-of rear myocardium tissue alpha expression of the present invention significantly reduces, and IL-10 expresses significantly to be increased, TNF-α/IL-10 ratio decline (table 2)
MRNA expression of cytokines change before and after table 2:MI 1 week of rat, the treatment at 4 weekends (x ± s)
Annotate: compare with sham operated rats (S group),
1)Expression P＜0.01,
2)Expression P＜0.05; Compare with the heart infarction matched group,
3)Expression P＜0.01,
4)Expression P＜0.05.
2.3 medicament adjusting MI rat heart muscle expression of myosin heavy chain mRNA of the present invention: MI
4Group α expression of myosin heavy chain mRNA is lower than S
4Group, the β expression of myosin heavy chain mRNA is higher than S
4Group, α MHC and β MHC ratio reduce.Drug therapy of the present invention can significantly increase the α expression of myosin heavy chain mRNA and reduce the expression of β myosin heavy-chain mRNA, also significantly rising (table 3) of α MHC and β MHC ratio simultaneously.
Table 3 medicine composite for curing of the present invention is to the influence of expression of myosin heavy chain mRNA (x ± S)
Annotate:
*Expression and S
4(sham-operation 4 all subgroups) group compares P＜0.01;
#Expression and MI
4(heart infarction 4 all subgroups) group compares P＜0.01.
2.4 pharmaceutical composition of the present invention significantly reduces MI rat matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) activity: Figure 3 shows that the activity of respectively organizing MMP-2 and 9.MI
4Group MMP-2 and 9 activity all are higher than S
4Group, medicine composite for curing of the present invention can significantly reduce the activity of myocardial infarction junctional area MMP-2 and MMP-9.
3 conclusions:, can reduce the myocardial cell proinflammatory factor and increase anti-inflammatory factors with traditional Chinese medicine composition for treating myocardial infarction of the present invention; Suppress the activity of regional myocardial matrix metalloproteinase 2 after the infarction and 9, destroy and the ventricular dilatation of carrying out property thereby reduce behind the myocardial infarction matrix metal proteinase activity extracellular matrix degradation, the heart support structure that causes that raise; Can reverse the change of myocardial myosin heavy chain gene phenotype in the myocardial remodelling process, produce the α MHC increasing expression of fast contraction, produce the β MHC expression decreased of shrinking at a slow speed, improve the contractile function of cardiac muscle on the whole.Traditional Chinese medicine composition for treating myocardial infarction of the present invention can obviously improve the maximum elevation rate of cardiac functional parameter such as LVED (Left Ventricular End Systolic Dimension), ejection fraction, shortening fraction and left ventricular pressure etc.
Description of drawings
Fig. 1: ultrasoundcardiogram changes before and after 1 week of MI rat, the treatment at 4 weekends.Annotate: ED=diastasis; The ES=end-systole.Picture shows that heart infarction group left ventricle enlarges markedly, especially 4 weekends; Can improve left ventricular remodeling behind the acute myocardial infarction after the Drug therapy of the present invention.
Fig. 2: myocardium pathological change: HE and immunohistochemical staining before and after the treatment of MI rat.Annotate: last figure leukocyte sxemiquantitative counting shows does not have significant difference between heart infarction group and the medicine group of the present invention (HE dyeing, X200); Figure below tumor necrosis factor and interleukin sxemiquantitative unit are integral optical density show between sham operated rats, heart infarction group and the medicine group of the present invention significant difference (immunohistochemical staining X400).
Fig. 3 Drug therapy of the present invention is to the influence of myocardium matrix metal proteinase activity.Annotate: sham-operation 4 all subgroup (S
4Group): n=12; Heart infarction group (MI group) and heart infarction-B organizes (MI-B group): n=15.A: statistical result:
*Expression and S
4Group compares, P＜0.05;
#Expression and heart infarction 4 all subgroup MI
4Group compares, P＜0.05; B: each organizes rat MMP2 and 9 gelatin zymogram band representative of graphics.
The specific embodiment
Embodiment 1: the preparation of medicine of the present invention
Prescription:
Radix Astragali 450g Radix Aconiti Lateralis Preparata 112.5g Radix Ginseng 225g Radix Salviae Miltiorrhizae 225g Semen Lepidii (Semen Descurainiae) 150g
Cortex Periplocae 180g Rhizoma Alismatis 225g Flos Carthami 90g Rhizoma Polygonati Odorati 75g Pericarpium Citri Reticulatae 75g Ramulus Cinnamomi 90g
Preparation method:
(1) Radix Astragali, Semen Lepidii (Semen Descurainiae), Rhizoma Alismatis, Radix Ginseng, Cortex Periplocae are added 8 times of amount 70% alcohol reflux 2 times according to above-mentioned prescription, 3 hours for the first time, 2 hours for the second time, merge extractive liquid,, filter, decompression filtrate recycling ethanol is concentrated into relative density and is the clear paste of 1.25-1.30 (60 ℃ of heat are surveyed), and is standby;
(2) Ramulus Cinnamomi, Pericarpium Citri Reticulatae distillating extracting oil proportionally, the aqueous solution of carrying behind the oil filters, and standby, residue adds 8 times of water gagings again and decocted 1 hour, filters, and merges decocting liquid, and is standby;
(3) Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Polygonati Odorati, Flos Carthami add 9 times of amount decoctions of water 2 times, each 2 hours, merge extractive liquid,, filter, merge with Ramulus Cinnamomi, Pericarpium Citri Reticulatae decocting liquid in the step (2), being concentrated into relative density is 1.25-1.30 (60 ℃ of heat are surveyed) clear paste, add ethanol in the stirring, left standstill below 70%, 4 ℃ 24 hours to determining alcohol, filter, decompression filtrate recycling ethanol, being concentrated into relative density is 1.25-1.30 (60 ℃ of heat are surveyed) clear paste, mixes 65-70 ℃ of oven dry with the alcohol extraction clear paste of step (1);
(4) dried cream mixed powder is broken into 100 order powder, adds 70% ethanol and granulates in right amount, sprays into Ramulus Cinnamomi, Pericarpium Citri Reticulatae volatile oil, and mixing is encapsulated, makes 1000, promptly.
Indication: be applicable to myocardial infarction, Heart Function After Myocardial Infarction is improved.
Usage and dosage: each 4, every day 3 times.
Claims (4)
1. the Chinese medicine composition application in the medicine of preparation treatment myocardial infarction is characterized in that described Chinese medicine composition made by following bulk drugs:
Radix Astragali 150-450 part, Radix Aconiti Lateralis Preparata 40-120 part, Radix Ginseng or Radix Codonopsis 75-225 part, Radix Salviae Miltiorrhizae 75-225 part, Semen Lepidii (Semen Descurainiae) 50-150 part, Cortex Periplocae or CORTEX ACANTHOPANACIS 60-180 part, Rhizoma Alismatis 75-225 part, Rhizoma Polygonati Odorati 25-75 part, Ramulus Cinnamomi 30-90 part, Flos Carthami 30-90 part, Pericarpium Citri Reticulatae 25-75 part.
2. application as claimed in claim 1 is characterized in that described Chinese medicine composition made by following bulk drugs:
450 parts of the Radixs Astragali, 112.5 parts of Radix Aconiti Lateralis Preparatas, Radix Ginseng or 225 parts of Radix Codonopsis, 225 parts of Radix Salviae Miltiorrhizaes, 150 parts of Semen Lepidii (Semen Descurainiae)s, Cortex Periplocae or 180 parts of CORTEX ACANTHOPANACIS, 225 parts of Rhizoma Alismatis, 75 parts of Rhizoma Polygonati Odorati, 90 parts of Ramulus Cinnamomi, 90 parts on Flos Carthami, 75 parts of Pericarpium Citri Reticulataes.
3. application as claimed in claim 1 or 2 is characterized in that, the active component of described Chinese medicine composition is made up of the effective ingredient that the following step makes:
1) with the Radix Astragali, Semen Lepidii (Semen Descurainiae), Rhizoma Alismatis, Radix Ginseng or Radix Codonopsis, Cortex Periplocae or CORTEX ACANTHOPANACIS with an amount of 70% ethanol extraction, filter, concentrated extracting solution is the clear paste of 1.25-1.30 to relative density;
2) volatile oil of extraction Ramulus Cinnamomi, Pericarpium Citri Reticulatae;
3) add suitable quantity of water and decoct Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Polygonati Odorati, Flos Carthami, obtained aqueous solution is filtered; The aqueous solution that Ramulus Cinnamomi, Pericarpium Citri Reticulatae are carried behind the oil filters, and collects aqueous solution filtrate, adds suitable quantity of water again and decocts residue, filters, and merges aqueous solution; The various aqueous solutions of above-mentioned gained are merged, and being concentrated into relative density is the 1.25-1.30 clear paste, adds ethanol in the stirring, to determining alcohol 70%, leaves standstill, and filters, and it is the 1.25-1.30 clear paste that filtrate is concentrated into relative density.
4. application as claimed in claim 1 or 2 is characterized in that, this Chinese medicine composition is capsule, tablet, electuary, powder or oral liquid.
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| CN102040641B (en) * | 2009-10-13 | 2014-10-29 | 河北以岭医药研究院有限公司 | Extraction separation method of pregnane glycoside in traditional Chinese medicine composition |
| CN102861230B (en) * | 2011-07-05 | 2014-05-28 | 河北以岭医药研究院有限公司 | Application of Chinese medicine composition in preparing medicines for treating organ fibrosis |
| CN102861231B (en) * | 2011-07-08 | 2015-06-17 | 石家庄以岭药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for treating ventricular remodeling after myocardial infarction |
| CN102895511A (en) * | 2011-07-28 | 2013-01-30 | 河北以岭医药研究院有限公司 | Application of Chinese medicine composition in preparing medicines for treating ischemic cardiomyopathy |
| CN102435734A (en) * | 2011-09-08 | 2012-05-02 | 大连医科大学 | Kit used for evaluating ovarian cancer primary chemotherapeutic sensitivity, and application thereof |
| TWI590830B (en) * | 2014-04-15 | 2017-07-11 | 財團法人工業技術研究院 | Active ingredients for enhancing stem cell differentiation and used in health care after recovery from myocardial infarction |
| CN104888177A (en) * | 2015-06-30 | 2015-09-09 | 德州学院 | Heart qi deficiency type ischaemic myocardial infarction treatment medicine compound and preparation method thereof |
| CN114404403B (en) * | 2021-12-27 | 2023-11-24 | 广州医科大学 | Application of alpinetin in preparation of medicines for treating myocardial infarction and myocardial remodeling after myocardial infarction |
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