Dissertation > Medicine, health > Pharmacy > Pharmacology > Experimental Pharmacology

The Protective Effect and Mechanism of L-carnitine Postconditioning on Myocardial Ischemical Reperfusion Injury in Rats

Author YaoLiHong
Tutor LuHong
School Liaoning Medical
Course Internal Medicine
Keywords Ischemia-reperfusion L-carnitine HSP70 apoptosis myocardial injury
CLC R965
Type Master's thesis
Year 2011
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ObjectiveEstablishing the myocardial ischemia-reperfusion model of rats.we observe the protection of L-carnitine postconditioning to rat,s myocardial ischemical reperfusion injury and explore its possible mechanism.MethodsThirty-two male SD rats were randomly divided into four groups(sham operation group;ischemical reperfusion group; ischemic postconditioning group and L-carnitine postconditioning group).They were marked by blank group,I/R group, postconditioning group and L-CN group.Each group has 8 rats. The rats in ischemica-reperfusion group were ligated the left anterior descending coronary(LAD) artery for 30 minutes,then removed the ligature to perfuse 120 minutes. The blank group was identical to the I/R group except that LAD was not ligated.The method of ischemic postconditioning is to open vascular which has ischemiaed 30 minutes to perfuse 10 seconds and ligate 10 seconds repeatedly for three times.The rest was the same with the I/R group.These three groups, rats were all injected 2ml saline into caudal vein at the equivalent of 5 minutes before reperfusion. The rats of L-CN group were treated with L-carnitine (400mg/kg,dissolved in 2ml saline) which were injected into caudal vein 5 minutes before reperfusion,modeling with the I/R group.At the end of reperfusion,we determined the serum , content of creatine kinase-MB(CK-MB),superoxide dismutase(SOD) and malondialdehyde(MDA). The pathomorphological changes were observed with optical microscope.The apoptosis number were determined with the method of TUNEL.We use immunohistochemistry to observe the expression of myocardial heat shock protein 70(HSP70) and phosphorylated c-Jun N-terminal kinase(pJNK).ResultsUnder the optical microscope,we can observe the histological morphology of myocardium dyed by HE in the blank group :cardiac muscle fibers were dyed uniformity, cells packed tightly and there were no vessel dilation and inflammatory cells infiltration in interstitial.Compared with the sham group,there were different degrees of injury in the I/R group, the postconditioning group and the L-CN group.Among these groups,the most heaviest damage appeared in the I/R group.The damage in the postconditioning group and the L-CN group were lessened than the I/R group with quite equal degree.The content of CK-MB levels were shown that:compared with the blank group, the I/R group, the postconditioning group and the L-CN group increased the content significantly (p<0.01);but the content of CK-MB in the postconditioning group and the L-CN group were significantly lower than the I/R group(231.25±23.75,239.00±17.98 VS 342.38±12.35)(p<0.01);there were no statistically significant difference in the postconditioning group and the L-CN group(p>0.05).Compared with the blank group,the activity of SOD was significantly lower in the I/R group, the L-CN group and the postconditioning group, the content of MDA was significantly higher,the differences were all statistically significant (p<0.01).To compare with the I/R group, the activity of SOD in the postconditioning group and the L-CN group increased obviously(61.17±4.71,62.38±7.22 VS 33.53±5.67),but still lower than that of the blank group,on the contrary, the content of MDA decreased obviously(8.81±0.36,8.93±0.34 VS 14.65±0.55)(p<0.01). The activity of SOD and the content of MDA had no statistically significant differences in the L-CN group and the postconditioning group(p>0.05).The apoptosis number and the expressiones of HSP70,pJNK in the I/R group, the L-CN group and the postconditioning group were higher increased than those in the blank group(p<0.01). Compared with the I/R group, the apoptosis number in the postconditioning group and the L-CN group (25.02±0.12,25.01±0.12 VS 33.18±0.11) and the expressiones of pJNK in the postconditioning group and the L-CN group(14.65±0.51,14.77±0.57 VS 20.58±0.38)decreased obviously(p<0.01), but still higher than those in the blank group, while the expressiones of HSP70 increased significantly(gray value decreased obviously)(121.04±0.33,120.93±0.22 VS 155.50±0.24)(p<0.01). In the postconditioning group and the L-CN group, the apoptosis number and the expression of HSP70,pJNK had no statistically significant differences(p>0.05).ConclusionL-carnitine postconditioning can reduce the release of CK-MB into the blood and lessen the myocardial pathological changes.It has obviously protective effect on myocardial ischemia-reperfusion injury just as ischemic postconditioning.It can significantly increase the activity of SOD, decrease the content of MDA,upregulate the expression of HSP70 and inhibit the phosphorylation of JNK to block the MAPK signaling pathway.The mechanism of the protection of myocardial ischemia-reperfusion injury may be related to anti-oxidation,anti- apoptosis effects.

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