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The Signal Transduction Of KaiXin Capsule On Ventricular Remodeling In Rat With Myocardial Infarction

Posted on:2008-12-07Degree:MasterType:Thesis
Country:ChinaCandidate:D ZhuangFull Text:PDF
GTID:2144360218961580Subject:Integrative Medicine Clinical Medicine
Abstract/Summary:PDF Full Text Request
BACKGROUNDAs the Intracoronary Ultrasound was developing, the death rate of AcuteMyocardial Infarction (AMI) was obviously decreased. When cordis confrontedMyocardial Infarction, the cardiac muscle will experience ventricle reconstruction; ithas become an importance reason that affects the prognosis of AMI.Kai Xin capsule make up with Powder for restoring pulse beat, Yue Ju Wan, Powder for Dissipating Blood Stasis. It was an empirical formula by Doctor Chen afamous veteran teran of TCM. Clinical application displays that Kai Xin capsule canamendment the cardiac reconstitution. Animal studies before has expressed that KaiXin capsule can amendment left ventricular chamber configuration of the myocardialinfarct rats when they are 8 weeks age, it can also amendment the interstitial collagen.The mechanisms may have something to do with the down regulation of AngⅡ,ALD and the mRNA expression of AT1 receptors, it may concerned with the decreaseof the c-los,c-jun,c-myc genes expression. The signal transduction of Kai Xincapsule has not study yet.There are many signal transductions that mediate cardiac ventriclesreconstitution, they influence each other, then consists complication information news. Great studies had indicated protein kinase C (PKC) is a center element of the signaltransduction which mediated myocardial hypertrophy and stimulate by myocardialhypertrophy factors. It may make an important role in hypertrophia of cadiocyte. PKCcan also activation Rafl in intracytoplasm, then associate with MAPKs pathway.MAPKs have been recognized as an identical pathway that many differentintracellular signals came through which caused hypertrophic cells and cellsmultiplication mediate by multiple extracellular signals. It conclude MAPKKK(Raf)→MAPKK(MEK)→MAPK(ERK) three parts. Activated MAPK cause themultiplication and vegetation through intranuclear transcription factors bytransmodulation. For this reason as the intranuclear signal transduction system, likeprotein kinase C and other signal transduction pathway mediate by MAPK, becomean importance study. Though thesis studies we may reveal the mechanisms of cardiacventricle reconstitution signal transductions.Our studies observed the cordiform and diastole contractile function of themyocardial infarction rats that were14 week's age after Kai Xin capsule treatment.Approach the effects that protein kinase C and the ERK1/2 had made in cardiacventricle reconstitution when they belong to the downstream signal factors of feritin-angiotensin system.ObjectiveTo investigate the effect of Kai Xin capsule on cordiform and diastole contractilefunctions in model of myocardial infarction rats when they were 14 week's age.Methods1. The manufacture and groups of the model of myocardial infarction ratsAdoption maleness Wistar rats, deligation left coronary artery main stem to setup 36 models of myocardial infarction rats. After operation given a electrocardiogramvery 10 min, as if appearance ST section raise successive 3 times then can document that is AMI, the model is successful. The group of sham operated has 12 models ofrats, the rest managements were the same with the group of AMI. After operation therats were given penicillin 40000U, by intramuscular injection 1 time everyday, totalthree days, all rats divide into three groups by random. The group of Kai Xin capsule, group of sham operated and group of captopril, group of control group. The group ofsham operated totally has 12 rats, except not deligation, they have the same treatmentas other group of rat. The group of Kai Xin capsule: intragastric Kai Xin capsule 10g/k g. d by liquid decoctum. The group of captopril: intragastric captopril 10ml/kgevery day by suspl. The group of sham operation: normally drinking water.2. Appreciation the heart function of myocardial infarct rats by DopplerechocardiographyAfter successive administration 14 weeks, appreciation the heart a function ofevery group of rats, the frequency of feeler is 12 MHZ; use classic left ventricle longaxis view, apex cordis fore chambers heart cross section, five chambers heart crosssection, at the same time recording ECG results. R wave represent end-diastole, Twave represent end-systole, carefully observed the shape of the heart and the motionrate of ventricular wall. Use method Simpsons determine ejection fraction (EF). Indexof morphology concludes: left ventricular end diastolic dimension (LVDd) and endsystolic diameter (LVDs), left ventricle end-diastole posterior thickness (LVPWd).Index of contractile function concludes: ejection fraction (EF), shortening fraction(FS). Compare the shape and heart function of every group of rats.3. The measure of heart quality/body constitutionsAfter the Doppler echocardiography, execute the rats. Before execute, measurethe rat's quality, washing-out the blood by cold physiological saline, use filter paperblot the water, measure the quality of rat's hearts. Calculate heart quality /bodyconstitution. Compare the level of cardiac enlargement in every group. 4. The cardiac muscle coloreturUse Mallory trichrome staining method color the cardiac muscle. Musclebecome yellow, interstitial collagen is bluish-green. Observing every group of rat bylight microscope, compare cardiac muscle desmophasia in.5. Effect of Kai Xin capsule on PKC in myocardial infarction ratsUse the un-radioalbumin PKC kit to detect the PCK contents in myocardialinfarction rats. To compare the PKC contents in each groups of rats.6. Effect of Kai Xin capsule on ERK1/2 actives in each groups of myocardialinfarction ratsTo observe Effect of Kai Xin capsule on ERK1/2 phosphorylation rat usedWestern Blot.7. Analysis of dataAll values are expressed as means + SD. Statistical analysis was performedusing SPSS 10.0 software. The differences between each sample were analyzed byone-way ANOVA. Statistical significance was defined as p<0.05.RESULTS1. The escape case of experimental animalDuring the lab process there are 2 rats die, 10 experiment rats rest in control group.There are 2 rats die, 10 experiment rats rest in sham operation group. There are 1 ratsdie, 11 experiment rats rest in captopril group. Totally there are 6 rats escaped, 42 ratsenter our experiment.2. The effect Kai Xin capsule on myocardial infarction ratsIndex EF and shortening fraction in control group are lower than other threegroups(P<0.01 ); end-systole PLV is higher than other three group. (P<0.01 );TheEF shortening fraction and PLV have no significant different in Kai Xin capsule group and captopril group, but the EF and shortening fraction in sham operationgroup are higher than Kai Xin capsule group (P<0.01).3. The effect of Kai Xin capsule on heart quality/body constitutions in experimentratsThe value of heart quality/body constitutions in control group is higher than otherthree groups (P<0.01), but the value between Kai Xin capsule group and captoprilgroup have no significant different (P>0.05).4. The effect of Kai Xin capsule on fibrotic cardiac muscle in experiment ratsBy the document of coloretur in cardiac muscle bindweb, the fibrotic extent inKai Xin capsule group and captopril group is lower than other group, but is higherthan sham operation group. The cardiac muscle fibril diastem is significantlywidening, cadiocyte hypertrophia, cardiac muscle fibril is severity, in control group.In sham operation group there is no collagen fibers hyperplasy, shape of cadiocyte isnormal, shade bank clearly resist, the structure is also normal.5. Effect of Kai Xin capsule on PKC in myocardial infarction ratsThe research show that PKC in control group is higher than the other threegroups (P<0.01), there is no significant difference in Kai Xin capsule group andcaptopril group (P>0.05).6.Effect of Kai Xin capsule on ERK1/2 actives in each groups of myocardialinfarction ratsThe phosphorylation rat of ERK1/2 in control group is higher than the otherthree groups (P<0.01),there is no significant difference in Kai Xin capsule group andcaptoprilgroup (P>0.05).CONCLUSIONS1. The model of acute myocardial infarction rats, by breeding 14 weeks, appearancemyocardial hypertrophy, and heart function decrease, cardiac muscular tissue fibrosis, so, it is a good model in cardiac ventricle reconstitution studies.2. Kai Xin capsule can improve model rats' heart function, lessen cardiac muscularfibrosis, and inhibit myocardial hypertrophy, the affect as captopril do.
Keywords/Search Tags:ventricular remodeling/ traditional Chinese medicine treatment, disease model, animal, protein kinase C/ analysis, Extracellular signalregulated kinase1/2 / analysis
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