Protective Effects Of Metallothionein On Myocardical Injury Induced By +Gz Stress And Its Mechanisms

Objective: To investigate protective effects of metallothionein (MT) on myocardical injury induced by +Gz stress and its mechanisms in rats. Methods: Twenty-four Wistar rats were randomly divided into control group, +Gz group and +Gz+MT group. +Gz Group and +Gz+MT group were exposed to repeated +10Gz stress, but control group was not submitted to +Gz stress. +Gz+MT group was given peritoneal injection of zinc lactate for inducing MT in vivo before +Gz stress while saline was given to the other two groups. The myocardial apoptosis were observed by electron microscopy and TUNEL detection. MDA, SOD, GSH-Px contents and Ca2+-Mg2+ -ATPase activity and mitochondrial PTP-opening in myocardium were measured by spectrophotometer. The myocardial Caspase-3, Bax, Bcl-2, PCNA, Ki67, Topoisomerase II a and the distribution of MT in myocardium were observed by imrnuno-histochemistry. The levels of MT in myocardium , liver and brain were tested by polarography. The myocardial P53 and NFkB were identified by Western blot analysis. Results: As compared with the control, the cell number of apoptosis , the contents of MDA ,Bax and P53 in myocardium were increased significantly in +Gz group. Mitochondrial PTP-opening induced by Ca2+ was much more in +Gz group than that in control group. The activities of SOD , Ca2+-Mg2+ATPase and the content of Bcl-2 were decreased significantly in +Gz group compared with those in control group (P<0.05) . In addition, Caspase-3, PCNA, Ki67, Topoisomerase II a were found positively in +Gz group. The changes mentioned above were improved in +Gz+MT group. There was no difference of the content of NFkB among three groups. Following +Gz stress the amounts of MT in myocardium, liver and brain were increased greatly. Conclusions: The results showed that +Gz stress could induce MT expression in heart,liver and brain. +Gz stress also could bring about disturbance in oxidative metabolism and lead to PTP-opening. The apoptosis induced by +Gz stress could be resulted from upregulate Caspase-3, Bax and P53. At the same time the proliferation in myocardium was accompanied. MT would be play protective effects by its antioxidant activity, increaseding activity of ATPase, restraining PTP-opening and suppress expression of promoting factors of apoptosis in myocardium.