Protective Effects Of Sesamin On Renal Fibrosis In Spontaneous Hypertensive Rats And Its Related Mechanism

Objective: To observe the protective effects of sesamin on renal fibrosis in spontaneous hypertensive rats(SHR) and its conceivable mechanism.Methods: SHR were randomly divided into sesamin of high and low dosages(160 and 80 mg·kg-1·d-1, n=7, respectively) groups, captopril(30mg·kg-1·d-1) positive control group, and SHR model(0.5% carboxymethylcellulose, 5ml·kg-1·d-1) group,body weight(220±10)g. In addition, the WKY(0.5% carboxymethylcellulose, 5ml·kg-1·d-1) negative control group was added. All animals were feded with these dosages daily for 12 weeks. Blood pressure(DBP) by tail cuff was measured every 2 weeks respectively. After 12 weeks, Body weight,left kidney and right kidney were weighed and kidney weight index was calculated respectively; levels of serum creatinine(Scr), blood urea nitrogen(BUN), urinary microalbumin(m Alb), 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 α-SMA andTGF-β1 positive cells in kidney were measured by immunohistochemistry. The expressions of a-SMA 、TGF-β1、p47phox、MMP-9、TIMP-1、AKT、p-AKT、 m TOR 、p- m TOR、4EBP1、S6K1、Bax and Bcl-2 proteins in kidney were detected by Western blot.Results:(1)Compared with WKY, DBP was significantly increased. SHR blood pressures were differently decreased after administration of sesamin.(2)The level of Scr 、BUN and m Alb were significantly increased in SHR, whereas those in all drug-treated groups were notably decreased.(3)The kidney weight index was markedly increased in SHR, and that in all drug-treated groups were lower than SHR.(4)Messangial matrix cells and basement membrane of glomerular were proliferated, and collagen deposition was appeared in the renal interstitium in SHR, while sesamin could ameliorate these pathological damages.(5) The level of MDA and expression of p47 phox protein in kidney were significantly increased, while the level of SOD was markedly decreased in SHR. However, sesamin could markedly decrease the level of MDA and expressions of p47 phox protein and increase the level of SOD as compared with SHR.(6)The protein and positive cells expressions of α-SMA and TGF-β1 in kidney were significantly up-regulated in SHR, while those of α-SMA and TGF-β1 were markedly down-regulated in sesamin groups.(7)The expressions of p-AKT、p- m TOR、4EBP1 and S6K1 proteins in kidney were significantly up-regulated in SHR. Nevertheless sesamin could markedly downregulate the expressions of AKT、p-AKT、m TOR 、p- m TOR、4EBP1 and S6K1.(8)The expressions of MMP-9 and TIMP-1 proteins in kidney were significantly up-regulated in SHR, while those of MMP-9 and TIMP-1 proteins were markedly down-regulated in sesamin groups.(9)The expression of Bax protein and apoptotic index in kidney was significantly increased, while the expression of Bcl-2 protein was markedly decreased in SHR. However, sesamin could markedly decrease the expression of Bax protein and apoptotic index and increase the expression of Bcl-2 protein.Conclusion: Sesamin has protective effect against renal fibrosis in spontaneous hypertensive rats. Its mechanisms may be related with anti-oxidization, down-regulating the expression of TGF-β1, reducing the production of α-SMA, inhibiting AKT/m TOR pathway, decreasing apoptotic index, restoring the MMP-9/TIMP-1 balance, up-regulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein.