Protective Effects Of Cordyceps Sinensis On Renal And Pancreatic Injuries Induced By Tacrolimus

Objective:To investigate the protective effect of Cordyceps sinensis(CS)on renal and pancreatic injury induced by tacrolimus(TAC)in rats and its mechanism.Methods:36 male SD rats were randomly divided into 4 groups(9 rats in each group),Normal control group:0.25 mL/kg/d olive oil was subcutaneously injected and normal saline1ml/kg/d was administered by gavage.CS group:CS 5g/kg/d was intragastric administration;TAC group:TAC 1.5mg/kg/d was subcutaneously injected and normal saline lml/kg/d was intragastric administration;TAC+CS group:TAC 1.5mg/kg/d was subcutaneously injected and CS 5g/kg/d was administered by gavage,4 weeks in each group.4 weeks later,The blood glucose was determined using by IPGTT,the Insulin concentration was measured by GSIS.The size of islets was detected by immunohistochemistry.The plasma 8-OHdG and urinary 8-OHdG excretion rate were determined by ELISA,The expressions of OPN,ED-1,WT1,MnSOD and Caspase-3 were detected by immunohistochemistry in renal tissue.Masson trichrome staining was used to observe TIF.The expression of MnSOD and Caspase-3 was detected by Western blot,and the TUNEL staining was used to observe the apoptotic cells in renal tissue.Results:1.Compared with the VH group,the body weight was significantly reduced in the TAC group,and the 24 hours urine volume and water intake,blood creatinine and urea nitrogen increased,p<0.05.Compared with TAC group,the body weight was significantly increased in the CS+TAC group,The serum creatinine and urea nitrogen decreased in CS+TAC group(p<0.05).2.Compared with VH group,the blood glucose in the TAC group increased significantly,the plasma insulin concentration and the size of the islets decreased significantly.Compared with the TAC group,the pancreatic function in the CS+TAC group improved significantly(p<0.05).3.Compared with the VH group,the expression of TIF and WT1 in the TAC group increased significantly.Compared with TAC group,the expression of TIF(10.8�2.4 vs 5.2�0.6)and WT1(15.8�0.6 vs 10.3�0.9,p<0.05)in CS+TAC group decreased significantly.4.Compared with the VH group,the expression of OPN and ED-1 in renal tissue of TAC group increased significantly;Compared with TAC group,the expression of OPN(9.3�0.8 vs 3.4�0.3)and ED-1(23.1�2.5 vs 14.8�1.8,p<0.05)in CS+TAC group decreased significantly.5.Compared with the VH group,Urinary 8-OHdG excretion rate and Serum 8-OHdG increased in TAC group;Compared with the TAC group,the Urinary 8-OHdG excretion rate(220.0�12.0ng/d vs 145.2�14.2ng/d)and Serum 8-OHdG(3c0.06ng/ml vs 1.34�0.05ng/ml,both p<0.05)decreased significantly.Compared with VH group,the expression of MnSOD in TAC group decreased,Compared with TAC group,the expression of MnSOD in CS+TAC group increased significantly(1.3�0.5 vs 5.6�0.7,P<0.05).6.Compared with VH group,the expression of Caspase-3 and the number of TUNEL positive cells in TAC group increased significantly,Compared with TAC group,the expression of both them decreased significantly in CS+TAC group(Caspase-3:8.9�0.8 vs 3.6�0.6,TUNEL:11.6�2.4cell/mm2 vs 5.2�1.2cell/mm2,p<0.05).Conclusion:1.The protective effect of Cordyceps sinensis on pancreatic injury induced by tacrolimus,and its mechanism is related to the improvement of beta cell function by Cordyceps sinensis.2.The protective effect of Cordyceps sinensis on renal injury induced by tacrolimus,the mechanism of which is related to the anti inflammation,anti fibrosis,anti apoptosis,anti oxidative stress and the impairment of podocyte in Cordyceps sinensis.