阿托伐他汀对肾大部切除大鼠残肾的影响

Effect of Atorvastatin on remnant kidney of rats with subtotal renal ablation

目的观察阿托伐他汀在肾大部切除大鼠模型中对残肾的保护作用并探讨其可能的机制。方法将32只大鼠随机分为4组,每组8只:假手术组、肾大部切除组、肾大部切除加小剂量阿托伐他汀组及大剂量阿托伐他汀组。8周后检测大鼠尿蛋白、肾功能和血脂;观察肾脏病理的改变;免疫组化检测FN在肾组织中的表达;并用RT-PCR测定肾组织中TGF-β1、CTGF和PAI-1mRNA的表达。结果治疗组大鼠尿蛋白定量、血BUN、Scr降低,FN表达下降,肾组织TGF-β1、CTGF和PAI-1mRNA的表达也下降,与肾大部切除组比较差异有显著性(P<0.01,P<0.05)。各组血脂水平无明显差异(P>0.05)。治疗组呈剂量依赖性使肾大部切除大鼠肾小球系膜细胞增生受抑制,肾组织胶原纤维沉积减少。结论阿托伐他汀可降低肾大部切除大鼠血BUN、Scr、尿蛋白,可抑制肾小球系膜细胞增生,减少系膜基质蓄积,且与血脂水平的改变无关,其肾脏保护作用可能与抑制肾组织CTGF、TGF-β1和PAI-1的表达有关。

[Objective] To investigate the nephroprotective effects of Atorvastatin on rats with subtotal renal ablation and its mechanism. [Methods] 32 Rats were assigned to four groups with 8 animals in each group： SHAM group, SNX group, LD group, and HD group. The urinary protein, BUN, Ser, serum total cholesterol, triglycerides and LDL were measured after 8 weeks. The expression of FN were detected immunohistochemicaUy. The expression of TGF-β1, CTGF and PAI-1 were detected by way of RT-PCR. [Results] After treatment with Atorvastafin, pro-teinuria, BUN and SCr in group LD and group HD were reduced in contrast to the group SNX （P〈0.01, P 〈0.05）. There were no significant changes in serum total CHOL, TG and LDL among the four groups （P 〉0.05）. Pathohisto-logical study revealed that there were less glomerular matris, collagen and fibroneetin in Atorvastatin treatment groups compared with the SNX group. There were less FN in two therapy groups than those in SNX group. Renal TGF-β1, CTGF and PAI-1 mRNA expression were markedly reduced in a dose-dependent manner in two therapy groups compared with the SNX group. [Conclusions] The urinary protein excretion,BUN and Scr in 5/6 nephrec-tomized rats were maybe decreased by Atorvastatin. And the renoprotective effect does not correlate with the change in serum lipid.Atorvastatin can rehve the glomerular sclerosis. This renoprotective effect may be attributed to inhibiting the expression of TGF-β1 , CTGF and PAI-1.