摘要
【目的】观察霉酚酸酯(MMF)对糖尿病大鼠肾组织中转化生长因子-β1(TGF-β1),p-Smad2/3表达的影响,探讨MMF对糖尿病肾病的保护作用及其机制。【方法】36只雄性SD大鼠随机分为正常对照组,糖尿病模型组和MMF治疗组,行单侧肾脏切除术,以链脲佐菌素(STZ)腹腔内注射建立糖尿病大鼠模型,药物干预后第4,12周每组处死6只大鼠,测24h尿蛋白定量,HE,Masson染色观察肾脏组织学改变;免疫组织化学方法检测TGF-β1,p-Smad2/3在肾组织中的表达。【结果】正常对照组有少量TGF-β1和p-Smad2/3表达,模型组大鼠24h尿蛋白排泄量增多(P<0.05),系膜区基质增多,TGF-β1和p-Smad2/3表达均明显增强(P<0.05);MMF治疗组24h尿蛋白排泄量显著下降(P<0.05),肾组织TGF-β1和p-Smad2/3表达均有减少(P<0.05)。【结论】在糖尿病大鼠模型中,MMF能下调TGF-β1,p-Smad2/3的表达,减少蛋白尿,延缓肾脏纤维化的进展,从而达到对糖尿病肾病的保护作用。
[Objective] To observe the expressions of TGF-β1 and p-Smad2/3 in renal tissue of diabetic rats intervened by mycophenolate mofetil (MMF), and to assess the effects of MMF on diabetic nephropathy model in rats, and to explore its mechanism. [Methods]Thirty-six male Sprague-Dawley rats were randomly divided into three groups: normal control group, diabetic model group and MMF-treated group. SD rats were made diabetic by intraperitoneal injection of streptozotocin after uni-nephrectomy, and the control group only injected the sham solution. Six rats of each group were sacrificed at the 4th week, 12th week, and 24hr urinary protein count was measured before dead. Rena pathological changes were investigated by HE and Masson staining. The expressions of TGF-β1 and p-Smad2/3 protein in renal tissue were detected by immunohistochemistry. [Results] The expressions of TGF-β1 and p-Smad2/3 were little in normal renal tissue. In diabetic model group, they were obviously higher than normal control group at each time point( P 〈0.05), and 24hr urinary protein count increased significantly( P〈0.05). The above mentioned parameters were all significantly inhibited after treated by MMF at each time point( P 〈0.05). [Conclusion] There are increased expressions of TGF-β1 and p-Smad2/3 in kidney of STZ-induced diabetic rats. MMF probably has some protective effect on diabetic kidney by inhibiting the TGF-β-dependent Smad signal pathway.
出处
《医学临床研究》
CAS
2008年第4期598-600,603,共4页
Journal of Clinical Research
基金
湖南省自然科学基金(05JJ30059)
作者简介
通讯作者,Email:zhanghaoliaoqing@163.com