Abstract:

Abstract:Objective To discuss the preventive effect of zinc preconditioning on renal ischemia-reperfusion injury (RIRI) in mice and provide experimental basis for prevention and treatment of RIRI  in clinic. Methods 50 male mice were randomly divided into 5 groups: sham operation group,RIRI model group,high dose zinc treatment group (60  mg•kg^-1),middle dose zinc treatment group (30  mg•kg^-1) and low dose zinc treatment group (15  mg•kg^-1),10 mice in each group. The mice in zinc treatment groups were administrated with ZnSO4 solution daily by gastric gavage for two weeks,while the equal volume normal saline was given to the mice in model group and sham operation group. Then the RIRI  model was prepared. After 30 min ischemia and 24 h reperfusion,the pathologic changes in kidney tissue of mice were observed by the method of HE staining;the apoptotic cells and the expression of c-fos were detected by TUNEL staining and immunohistochemistry,respectively. Results The pathohistological results showed the pathological changes in kidneys of mice in model group,such as tubular dilation with cast formation,vacuolization and necrosis of renal tubular epithelial cells in renal cortex,the more serious changes occurring in the location between cortex and medulla with severe blood congestion and necrosis region. The mice in high dose zinc treatment group appeared the above pathological changes. In middle dose and low dose zinc treatment group,the abov changes were improved,which were swelling of renal tubular epithelial cell,less congestion and cell necrosis in the location between cortex and medulla. The pathological  improvement in low dose zinc treatment group was better than that in middle dose zinc treatment. TUNEL staining showed that the number of apoptotic cells in model group was significantly higher than those in middle and low dose zinc treatment group（P<0.05）,and the number of apoptotic cells in low dose zinc treatment group was significantly lower than that in middle dose zinc treatment group（P<0.05）. The immunohistochemical results showed that compared with sham operation group,the c-Fos-positive cell rates in model group and zinc treatment groups were significantly increased (P<0.01);compared with model group, the c-Fos-positive cellrate in middle and low dose zinc treatment groups were significantly decreased (P<0.05);the c-Fos-positive cell rate in low dose zinc treatment group was significantly lower than that in middle dose treatment group (P<0.05). Conclusion Zinc sulfate has a protective effect on RIRI  in a certain dosage range and the possible mechanism may be associated with the decreasing of apoptotic cells and  c-Fos expression induced by zinc.

Key words:  zinc;ischemia-reperfusion injury;apoptosis;c-fos；HE staining