| Objective To investigate the nephroprotective effects of atorvastatin on rats with subtotal renal ablation and its mechanism.Methods 32 Rats were ran domly assigned to four groups with 8 animals in each group: Sham-operated (SHAM), subtotal renal ablation(SNX), SNX treated with low dose atorvastatin ((8mg·kg-1·d-1)) (LD), and SNX treated with high dose atorvastatin (16mg·kg-1·d-1 (HD). The urinary protein, BUN, serum creatinine(Scr), serum total cholesterol, triglycerides and LDL were measured after 8 weeks. Blood pressure and renal pathological changes were evaluated. The expression of TGF-β1 and FN were detected immunohistochemically. Renal collagen fibers were stained with Picric acid-Sirius red. The expression of TGF-β1, CTGF and PAI-1 were detected by way of RT-PCR.Results(1) The rats in SNX group manifested progressively increasing prteinuria, BUN and Scr (P＜0.01). After treatment with atorvastatin, proteinuria, BUN and SCr in group LD and group HD were reduced in a dose-dependent manner in contrast to the SHAM operation group(P＜0.05). There were no significant changes in serum total CHOL, TG and LDL among the four groups.(2) Systolic BP was significantly increased in group SNX 8 weeks after subtotal renal ablation. The increases in SBP were significantly blunted in group LD and group HD (P＜0.05).(3) Pathohistological study revealed that there were less glomerular matris, collagen and fibronectin in Atorvastatin treatment groups compared with the SNX group. Among the 5/6 nephrectomized rats, HD group had the least renal changes in collagen and fibronectin deposition. There were less TGF-β1 and FN in two therapy groups than those in SNX group. (P＜0.05, P＜0.01) The changes in HD group was more dignificant.(4) The expressions of renal TGF-β1 mRNA,CTGF mRNA and PAI-1 mRNA in the SNX group were higher than that in the SHAM group (P＜0.01). Renal TGF-β1 and PAI-1 mRNA expression were markedly reduced in a dose-dependent manner in two therapy groups compared with the SNX group (P＜0.05).Conclusions(1) The urinary protein excretion in 5/6 nephrectomized rats was maybe decreased by atorvastatin in a dose-dependent manner and decreased renal damage. And the renoprotective effect does not correlate with the change in serum lipid.(2) The blood pressure in chronic renal failure rats was maybe obviously cut down by atorvastatin.(3) Atorvastatin may reduce the expression of renal fibronectin and FN in subtotal nephrectomy rats.As a result, Atorvastatin can relive the glomerular sclerosis.(4) Atorvastatin may inhibit the expressions of TGF-β1 mRNA ,CTGF mRNA and PAI-1 mRNA in a dose-dependent manner. This renoprotective effect may be attributed to inhibiting the expression of TGF-β1, CTGF and PAI-1. |
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