霉酚酸酯对UUO大鼠肾间质p-Smad2/3表达的影响

Effect of Mycophenolate Mofetil(MMF) on the Expression of p-Smad2/3 in Unilateral Ureteral Obstruction(UUO) Rats

【目的】通过霉酚酸酯(MMF)干预单侧输尿管梗阻(UUO)大鼠模型,动态观察TGF-β1、p-Smad2/3在梗阻侧肾组织中的表达,探讨MMF对TGF-β依赖性Smad信号通路的影响。【方法】54只雄性SD大鼠随机分为假手术组(SOR组)、UUO组和MMF组。于术后d7、d14、d21每组分别处死6只大鼠。HE、PAS和Masson染色观察梗阻侧肾间质胶原相对面积和炎症细胞浸润指数的变化,免疫组化染色法观察TGF-β1和p-Smad2/3蛋白在肾间质中的表达,RT-PCR方法观察TGF-β1在肾组织中的表达。【结果】UUO组肾间质胶原相对面积、炎症细胞浸润指数、TGF-β1和p-Smad2/3蛋白表达,以及肾组织TGF-β1mRNA表达均较SOR组显著增高,MMF组各时间点与相应UUO组比均显著降低。【结论】MMF能通过抑制TGF-β依赖性Smad信号通路延缓UUO大鼠肾间质纤维化的进展。

[ObjectivelTo explore the effect of MMF on the TGF-β -depended Smad signal pathway in the obstructive renal tissue of UUO rats. [MethodslFifty-four male Sprague-Dawley rats were randomly divided into three groups： sham-operated rats （SOR） group, UUO group, MMF group. Six rats in each group were sacrificed at the 7th, 14th, 21th day after operation. The collagen area and the index of cell infiltration were observed by HE, PAS and Masson stain. The protein expressions of TGF-β1 and p-Smad2/3 in renal interstiti- um were detected by immunohistoehemistry. The mRNA expressions of TGF-β in renal tissue were observed by RT-PCR. [ResultslThe collagen area, index of cell infiltration, protein expressions of TGF-β1 and p- Smad2/3, and the mRNA expressions of TGF-β1 in group UUO were obviously higher than in group SOR. They were decreased in group MMF at each time point. [ConelusionlIn UUO rats, MMF may postpone renal interstitial fibrosis by inhibiting the TGF-β-depended Smad signal pathway.