| Objective: To observe the protective effects of sesamin combined with vitamin E on renal fibrosis in spontaneous hypertensive rats(SHR)and its potential mechanism.Methods: SHR were randomly divided into sesamin(160 mg·kg-1)groups,vitamin E(10 mg·kg-1)group,sesamin(160 mg·kg-1)combined with vitamin E(10 mg·kg-1)group and SHR model(0.5% carboxymethylcellulose)group.In addition,the WKY rats were given 0.5% carboxymethylcellulose as negative controls.The amount of all groups was 8 respectively,and the body weight of all rats was selected in the range of(190±10)g.All animals were administered intragastrically the corresponding drugs once a day.Blood pressure by tail cuff was measured every 2 weeks respectively.After 10 weeks,body weight,left kidney and right kidney were weighed and kidney weight index was calculated respectively.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),urinary microalbumin(U-m Alb),serum β2-microglobulin(β2-MG),superoxide dismutase activity(SOD)and malonic dialdehyde(MDA)were measured by automatic biochemical analyzer.The primary pathologic changes and collagen deposition of kidney were observed by hematoxylin and eosin stain(HE)or Masson staining.The expressions of TGF-β1 and CTGF positive cells in kidney were measured by immunohistochemistry.The protein expressions of TGF-β1、Src、pY416Src、ERK1/2、p-ERK1/2、EGFR、p-EGFR、p-Smad2/3 in kidney were detected by Western blot.Results:(1)Compared with WKY,SBP、DBP and MAP was significantly increased in SHR.The blood pressures were differently decreased after administration.As compared with ses or VE,SBP、DBP and MAP of ses+VE group were significantly decreased.(2)The levels of Scr、BUN、β2-MG and U-mAlb were significantly increased in SHR,whereas those in all drug-treated groups were notably decreased.Compared with ses or VE group,the levels of Scr、BUN、β2-MG and U-mAlb of ses+VE group were markedly decreased.(3)The kidney weight index was apparently increased in SHR,and those in all drug-treated groups were lower than that of SHR.(4)Basement membrane of glomerular were proliferated,and collagen deposition was appeared in the renal interstitium in SHR,while administration could ameliorate these pathological damages,especially in combination drug group.(5)The content of MDA in kidney was significantly increased with the level of SOD markedly decreased in SHR.However,drug treatment obviously decreased the level of MDA and increased the level of SOD as compared with those of SHR.The above mentioned effects were significantly strengthened in combination drug group.(6)The protein and positive cells expressions of TGF-β1 and CTGF in kidney were apparently up-regulated in SHR,while those were markedly down-regulated in administration groups.The effects were significantly enhanced in combination drug group.(7)The protein expressions of TGF-β1、p Y416Src、p-EGFR、p-ERK1/2、p-Smad2/3 in kidney were obviously up-regulated in SHR.Nevertheless drug treatment could markedly downregulate these protein expressions.Furthermore,the effect of combination drug group was significantly better than that of sesamin or vitamin E group.Conclusion: Combination of sesamin and vitamin E could synergistically develop protective effect against renal fibrosis,which was significantly better than that of single drug treatment.The ameliorative effects may be related to decreasing blood pressure,increasing anti-oxidative stress,downregulating over-activated TGF-β1,restraining the expressions of Src/EGFR/ERK signal pathway and TGF-β1/Smad2/3 signal pathway. |
