| Objective:To investigate the protective effect of Shen-kang injection(SK)on tacrolimus(TAC)induced renal injury and its mechanism.Methods:36 male Sprague Dawley(SD)rats were randomly divided into 4 groups(9 in each group).The VH group rats were subcutaneous injected with olive oil 0.25 mL/d,and intraperitoneally(IP)injected with 1 mL/d saline.The SK group rats were subcutaneous injected with olive oil 0.25 mL/,and IP injected with SK 1 mL/d.The TAC group rats were subcutaneous injected with TAC 1.5mg/kg/d,and IP injected with 1 mL/d saline subcutaneous injection,and saline intraperitoneally injection;The TAC+SK group rats were subcutaneous injected with TAC 1.5mg/kg/d,and IP injected with SK 1 mL/d saline.The rats were treated for 4week's.The body weight of rats were measured every week after the start of the experiment,the rats were placed in metabolic cages after 4 week's treatment and measured the water intake and 24 hours urine output,then collect the urine and blood samples.The rats were sacrificed extraction of renal tissue.The levels of serum creatinine and urea nitrogen were measured by automatic biochemical analyzer.The 8-OHdG of urine was measured by ELISA.The index GSI of glomerular basement membrane was observed by PAS staining.Masson staining was used to observe the degree of TIF.The expression of ED-1?OPN?WT-1?8-OHdG?MnSOD and Caspese-3 was determined by immunohistochemical staining.The expressions of TGF?-1?Caspase-3?MnSOD?Bcl-2 and Bax were measured by immunoblotting.TUNEL staining was used to observe the apoptotic cell death.Results:1.Compared with the VH group,the body weight was decreased and the 24 hours of water intake and urine volume was increased in the TAC group.Compared with the VH group,the Ccr was decreased in the TAC group,Administration of SK was significantly increased Ccr(0.5±0.04 vs 0.6±0.03,P<0.05)level.2.Compared with the VH group,the degree of TIF,the number of PAS positive cells and TGFp-1 expression was increased in TAC group,but SK treatment was significantly decrease the degree of TIF,PAS positive cells and TGF?-1(TIF:11.8±2.5%vs 4.6±0.8%,P<0.05)?(TGF?-1:1.6±0.10%vs 1.0±0.05%,P<0.05)?(PAS:17.3±2.4%vs 12.1±1.8%,P<0.05);3.Compared with the VH group,TAC treatment was decreased WT-1 expression,but the SK treatment was increased the WT-1 expression.4.Compared with the VH group,the number of ED-1 positive cells and OPN was significantly increased in TAC group,but the SK treatment was decreased the number of ED-1 positive cells(23.2±2.3 vs 15.1±2.1,P<0.05)and OPN.5.Compared with the VH group,the 8-OHdG level increased in urine and kidney,but the SK treatment was decreased 8-OHdG level in ureine and kidney(urine8-OHdG:230±14vs 162±17,P<0.05)(kidney8-OHdG:15.7±2.3%/mm2 vs 8.9±1.4%/mm2,P<0.05).The TAC treatment was decreased expression of MnSOD,but administration of SK significantly increased expression of MnSOD.6.TAC treatment was increased Caspese-3 expression and decreased the Bcl-2/Bax ratio,but the SK treatment was decreased Caspasp-3 and incrased the ratio of Bcl-2/Bax(0.1±0.01 vs 1.0±0.02,P<0.05).7.Compared with the VH group,the TAC treatment was increased the number of apoptotic cells,but the SK treatment was significantly decreased the number of apoptotic cells(10.2±2.0/mm2 vs 4.6±1.8/mm2,P<0.05).Conclusion:SK has a good protective effect on TAC-induced renal injury,and its mechanism may be related to SK inhibition of inflammation,anti-oxidation,inhibition of apoptosis and interstitial fibrosis. |
PDF Full Text Request