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Protective Effects Of L-carnitine Against Simulated Ischemia And Reperfusion Injury In Cultured Neonatal Rat Cardiomyocytes

Posted on:2005-02-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y YangFull Text:PDF
GTID:2144360122490216Subject:Internal Medicine
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BackgroundCarnitine,presents in various tissues and cells investigated thus far. It plays a role in carrying long chain fatty acids across mitochondial membrane to accelerate tricarboxylic acid cycle and fulfill the normal physiological function and energy metabolism in cell.With its specific biochemistry function,carnitine can save a amount of substrate of energy metabolism and improve enzyme activity and oxidation of glucose and clear lactic acid in pathophysiologic course.Now carnitine has already been widely focused and used in most human metabolic diseases and related diseases,such as carnitine palmitoyltransferase type II deficiency N HIV-infected children on antiretroviral treatment % dialysis-related carnitine deficiency syndrome% chronic viral hepatitis > ischemic cardiovascular cerebrovascular diseases.The injury during ischemia/reperfusion is nonspecific.It will cause the accumulation of many metabolic products,such as lactic acid, protons Pi and adenosine, and the loss of metabolic substrate,the decrease of heart function and the overload of Ca2+ and free radical. What's more,the cascade effect of free radical and the overload of Ca2+ have close relationship with cell apoptosis.Recent studies haveindicated that carnitine has protective effects against the harm caused by radicals.But up to now,there are few reports on the protective effects of carnitine in cardiomyocytes with such conditions.And the aim of the experiment is to evaluate the effect and study the mechanism elementarily. MethodsThe main topic is to evaluate the protective effect of carnitine on cultured neonatal rat cardiomyocytes after I/R. Cardiomyocytes were obtained from neonatal rats, primarily cultured and were dealt with by the simulated I/R instruments.The cells were divided into 3 groups: control group, I/R group (I:120min, R:240min),L-C group(L-carnitine was added into the medium 2h beforehand).In L-C group, there were 4 subgroups and the 1-carnitine concentration was Igroup20 mg/L, II group 50 mg/L , III group 100 mg/L , IV group 200 mg/L respectively.The activity of SOD and the amount of MDA were evaluated after the experiment.The apoptosis rate of cardiomyocytes was measured by FCM.The morphologic characteristics were observed by TEM.At the same time,we also evaluate the activity of SDH and observe the changes in morphology of mitochondrion.The data was calculated by SPSS. Results and Conclusionsl.I/R group showed more decrease of SOD and SDH activities and increase of MDA compared with the control group(P<0.05),and at the same time, the apoptosis rate was increased more sharply (P<0.05).ln L-camitine group, the activities of SOD and SDH were significantly increased but the apoptosis rate and MDA were decreased little by little with the incrase of the concentration of L-carnitine.And ascompared with I/R group,there was statistical significance((P<0.05).2.1mages: Cardiomyocytes had wonderful structures and the mitochondrion keeps complete and chromatin was well-distributed in control group. In I/R group, the apoptotic changes were characterized by shortening and decreasing of processes,cell shrinkage,compact of cytoplasm with emergence of many vacuoles,nuclear condensation.In L-C group,the injury in the sub-structure of cardiomyocyte was lessened compared with I/R group.The mitochondria cristae was partly disorganized.3.(1)L-carnitine can protect cardiomyocyte from LPO injury and apoptosis and the protective effect was in a dose-related manner within certain concentration.(2)From the photos ,we can find that 1-carnitine can improve cell apoptosis and lessen the morphological changes of mitochondria and modulate the energy metabolism of cells in such conditions.
Keywords/Search Tags:L-carnitine, ischemia/reperfusion, free radical, apoptosis, energy metabolism
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