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The Complement Activation And Drug Intervention In Rats With Acute Myocardial Infarction

Posted on:2012-12-25Degree:MasterType:Thesis
Country:ChinaCandidate:X Y LiuFull Text:PDF
GTID:2214330335498972Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:To define whether the complement system is activated and whether there is the relationship between the degree of complement system activation marker complement 3(C3),the membrane attack complex(C5b-9)and myocardial damage in rats with acute myocardial infarction (AMI) and the effects of early fluvastatin and Qishengyiqi extractive intervention on complement system activation and cardiac function and explore the potential mechanism.Methods:1.The 70 male Wistar rats were randomly divided into 5 groups:the control group(A, n=10) rats were fed routinely 7 days without medicine intervention;sham operation group(B,n=12)rats were fed routinely 7 days before sham operation without medicine intervention;the acute myocardial infarction group(C, n=18) rats were fed routinely 7 days before AMI operation without medicine intervention;the Qishenyiqi extractive group(D, n=15) rats were treated with Qishenyiqi extractive 100mg/Kg/d 7 days before AMI operation; the fluvastatin group(E,n=6), rats were treated with fluvastatin 4mg/Kg/d 7 days before AMI operation.2.The experimental AMI model of Wistar rats was established by ligation of left anterior descending branch of coronary artery.3.Hemodynamic evaluation were underwent just 24h after coronary ligation or sham operation and recorded the following parameters:HR, SBP, DBP, MBP, LVSP, LVEDP,+dp/dt max,-dp/dt max.4.Collect blood 2ml by aortic puncture and centrifugate all blood samples by 2000r/min in 15 minites, serum stored at low temperature freezer(-80℃), assay of soluble complement form of C3 and C5b-9 by enzyme-linked immunoassay(ELASA).5. After hemodynamic evaluation, rats were killed by injecting 10% Kcl solution 2-3ml when cardiac arresting in diastole.Take the heart, remove the left atrium and right atrium, the heart is divided into two parts of the left ventricle and right ventricle,respectively the weight of left ventricle(LVw) and right ventricle(RVw) divided by the weight is coming left and right ventricular relative weight((LVw/Bw,RVw/Bw).6. The heart samples were collected were then separately fixed in 10% formalin saline,dehydrated through graded alcohol series,cleared in xylene and embedded in paraffin wax(melting point 56℃).Serial section of 5μm were cut, stained with hematoxylin and eosin(HE) and used for the assessment of histopathologial changes.7.Immunohistochemical studies on the levels of the uninfarct,infarct border zone,infarct heart tissues were found to be positive for C5b-9 deposition, application imagepro plus software for quantitative analysia about these.Results:1.All rats in groups A and B (n=12) were survrived; 9 rats were survived in group C, the success rate of operations was 50%; 9 rats were survived in group D, the success rate of operations was 60%; 12 rats were survived in group E, the success rate of operations was 80%. There were no significant differences in regard to survival rate among the three groups (P>0.05).The success rate of all AMI operations was 62.5%.2.The SBP,MBP,+dp/dt max,-dp/dt max in AMI model groups were significantly lower than those in group A and B (P<0.05);those in group D and E were higher than those in group C (P<0.05), There were no statistical differences between group D and E (P>0.05); The LVEDP in AMI model groups were significantly higher than those in group A and B (P<0.05);compared with group C, the LVEDP in group D and E were significantly reduced(P<0.05), there were no statistical differences between group D and E (P>0.05).3.The levels of C3 and C5b-9 in AMI model groups were significantly elevated than that in group A and B in serum (P<0.05), compared with group C, the levels of C3 and C5b-9 in group D and E were significantly lower (P<0.05), there were no statistical differences between group D and E (P>0.05).4.no complement deposite in normal myocardial;compared with group, C,the C5b-9 in group D and E were significantly reduced in infracted region and border zone (P<0.05),there were no statistical differences between group D and E(P>0.05).Conclusions:1.Complment system activate after AMI in rats,the levels of C3,C5b-9 in serum and C5b-9 deposition in infarcion heart tissues and infarct border zone were found to be significantly elevated.2.Short-term pre-intervention with fluvastatin and Qishengyiqi extractive could clearly inhibit complment system activation after AMI in rats, reduce the levels of C3,C5b-9 in serum and decrease C5b-9 deposition in infarcion heart tissues and infarct border zone.3.Short-term pre-intervention treatment with fluvastatin and Qishengyiqi extractive can reduce myocardial infarction by inhibiting complment system activation,therefor improved cardiac fucution and the ealy left ventricular remodeling.
Keywords/Search Tags:Fluvastatin, Qishengyiqi extractive, Acute myocardial infarction, complement 3, complement 5b-9
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