The Effect Of Antioxident Therapy On Renal Interstitial Fibrosis In Hyperlipidemia Rats

Objective: Tubular formation and interstitial fibrosis are crucial phenomena in the progressive deterioration of renal function in the course of renal diseases. Moreover, interstitial fibrosis has long been recognized as a main prognostic factor regarding renal function outcome in both human glomerular and tubulointerstitial nephropathies. Experimental evidence suggests that abnormalities in lipid metabolism appear to play a important role in progression of renal interstitial fibrosis. VLDL, LDL, Ox-LDL all can result in mesangial cellular proliferation and renal interstitial fibrosis. In particular, oxidized LDL(Ox-LDL)may play an important role in the pathogensis of chromic renal failure associated with hyperlipidmia. The slight elevation in serum LDL+VLDL observed in the hyperlipidmic rats might contribute to increasee in LDL oxidation in the kidney and enhance the infiltration of macrophages into glomeruli.Ox-LDL is noteliminated by the hepatic native LDL receptor system. Instead, these modified lipoproteins bind to a family of scavenger receptors that includes macrophage type-I and type-II scavenger receptors,et al. Uptake of oxidized LDL by scavenger may trigger a cascade of responses leading to fibrogenesis.Probucol is a bisphenolic compound that lowers serum cholesterol level and has also been shown to be a potent antioxidant. It has been found to partially prevent the decrease in GFR and renal plasma flow observed after ureteral obstrution in rats. Although probucol reduces high-density lipoprotein cholesterol level, the marked antiatherogenic effect of the agent has been attributed to its property to decrease or prevent the oxidization of LDL cholesterol. Reduction of oxidation of LDL may prevent macrophage infiltration of the renal parenchyma in pathophysiologic states. VitE is a antioxidant too. The present studies were designed to study whether antioxidant therapy (Probucol+VitE) could attenuate interstitiall fibrosis in hyperlipidmic rats and to observe changes in the pattern of renal cytokine expression induced by antioxidant therapy.Methods: We performed a left nephrectomy on Thirty female Sprague-Dawley rats five days the study began. The rats were randomly divided into three groups. There were 10 rats in every group. The control group was fed standard rat chow. The high-lipid diet groupwas fed standard chow supplemented with 1.5% cholesterol, 0.5% cholic acid and 5% lard. The treatment group was fed the same high-cholesterol diet supplement, with the treatment of 50IU/d vitamin E and 500mg/d probucol. At 12 weeks all animal were killed. Renal function and MDA were measured by biochemical studies. The expression of collagen I and transforming growth factor- P ,(TGF- ?,) were examined by immnohistochemistry.Results: (1) Rats fed a high-lipid diet elevated significantly the level of serum cholesterol compared with rats fed standard chow(po.Ol) and rats treated by antioxidant therapy(po.01). The level of serum triglyceride were higher in the highlipid diet group and the treatment group compared with the control group(po.01), but there were no significant difference in the former two groups. (2) Serum creatinine were significantly higher in the high-lipid diet group than that in the control group(po.01). Creatinine clearance rates were significantly lower in the high-lipid diet group. Serum creatinine were significantly lower and creatinine clearance rates were significantly higher in the treatment group compared with high-lipid diet group(po.05).(3) The level of MDA in renal interstitium were significantly lower in the treatment group compare with the high-lipid diet group(po.01). But there were no difference between the treatment guoup and the control group. (4) The degree of renal interstitialchronicity lesion in the treatment group increased significantly compared with the control group(po.01), and decreased significantly compared with the high-lipid diet group.(5) The expressions of collagen I and TGF- (3 , in the treatment group were lower compared with the high-lipid...