Study Of Exercise Fatigue-induced Cardiac Myocytes Apoptosis Through20-HETE,and PKC

Exercise fatigue refers to the body’s function cannot maintain a certain scheduled level or exercise intensity. The mechanism that causes exercise fatigue is complex and multiple organs are involved in it.20-Hydroxyeicosatetraenoic acid (20-HETE), a metabolic product of arachidonic acid catalyzed by cytochrome P450ω-hydroxylase, is a kind of important vasoconstrictor. In order to reveal the effect of the release of endogenous substances20-HETE on the cardiac myocytes apoptosis induced by exercise fatigue. In addition, whether PKC was activated by exercise fatigue and induced cardiac myocyte apoptosis was also discussed. We designed the following experiment to explore the effects of exercise fatigue on cardiac myocytes apoptosis and its mechanism. The rats were randomly divided into4groups:control group, exercise group, exercise fatigue+20-HETE inhibitor HET0016group and exercise fatigue+PKC inhibitor chelerythrine (CHE) group. The rats in control group daily intraperitoneal injected with physiological saline1ml.Rats in the rest three groups were intraperitoneal injected with normal saline, HET0016(lmg/kg) and CHE (5mg/kg) respectively10min before every swimming training, followed by swimming fatigue training for15days. Experiment methods and results are as follows:(1) The morphological changes of nucleus was detected by Hoechst staining, and we found that compared with the control group, myocardial nuclear volume was significantly minished and nucleus pyknosis was appeared after exercise fatigue; But the phenomenon of karyopyknosis was obviously inhibited by intraperitoneal injecting of20-HETE synthesis inhibitor HET0016or PKC inhibitor chelerythrine (CHE) before exercise.(2) Cardiac myocytes apoptosis was measured by TUNEL, the apoptosis rate of cardiac myocytes in the exercise fatigue group was significantly increased by14.3%; But the rates of apoptosis in both exercise fatigue+HET0016group and exercise fatigue+CHE group were significantly decreased (6.82±0.72%and7.12±0.67%, respectively).(3) The mRNA expression of anti apoptosis protein Bcl-2and pro apoptotic protein Bax were detected by RT-PCR and exercise fatigue significantly increased the expression of Bax mRNA and the Bcl-2mRNA level was decreased compared with control. While the following changes induced by exercise fatigue were obviously inhibited by intraperitoneal injecting of HET0016or chelerythrine (CHE) before exercise.The results indicated that, the exercise fatigue induced cardiomyocyte apoptosis. and exercise fatigue can promote the release of myocardial endogenous substance20-HETE and activate PKC, and thus causing the occurrence of cardiac myocytes apoptosis.