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目的探讨霉酚酸酯(MMF)对糖尿病大鼠肾小管上皮细胞转分化的影响及其可能机制。方法雄性SD大鼠28只,随机选取8只作为正常对照组(N组),其余20只注射链脲佐菌素(STZ)制作糖尿病模型,并随机分为糖尿病组(DM组)、霉酚酸酯组(M组)。12周后测量大鼠血糖、体质量、肾质量/体质量、24 h尿蛋白定量、血肌酐(SCr),观察肾小管间质病理形态学变化,应用免疫组化技术和Western blot检测肾组织中α-平滑肌肌动蛋白(α-SMA)及转化生长因子β1(TGF-β1)的表达。结果 DM组血糖、肾质量/体质量、24 h尿蛋白定量、血SCr、肾小管-间质损伤指数(TII)均明显高于N组(P<0.01),M组除血糖、体质量外(P>0.05),其余指标均明显低于DM组(P<0.01);免疫组化结果显示,DM组肾小管上皮细胞胞浆中α-SMA、TGF-β1表达均明显高于N组(P<0.01),M组明显低于DM组(P<0.01);Western blot结果显示,DM组肾组织α-SMA、TGF-β1表达较N组分别增加3.4倍与1.1倍,M组肾组织α-SMA、TGF-β1表达较DM组分别下降55%与40%。结论 MMF能下调糖尿病大鼠肾小管上皮细胞α-SMA、TGF-β1的表达,抑制肾小管上皮细胞转分化,起到肾脏保护作用。
Objective To investigate the effect of mycophenolate mofetil (MMF) on renal tubular epithelial cell transdifferentiation in diabetic rats and its possible mechanism. Methods Totally 28 male Sprague-Dawley rats were randomly divided into normal control group (n = 8) and 20 diabetic rats injected with streptozotocin (STZ), and were randomly divided into diabetes group (DM group), mycophenolate mofetil Acid ester group (M group). After 12 weeks, blood glucose, body weight, kidney mass / body weight, 24 h urinary protein and serum creatinine (SCr) were measured to observe the pathological changes of tubulointerstitial. Immunohistochemistry and Western blot were used to detect the changes of renal tissue Alpha-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) expression. Results The blood glucose, kidney mass / body weight, 24 h urinary protein, blood SCr and tubulointerstitial injury index (TII) in DM group were significantly higher than those in N group (P <0.01) (P> 0.05), and the other indexes were significantly lower than those in DM group (P <0.01). The results of immunohistochemistry showed that the expression of α-SMA and TGF-β1 in the cytoplasm of renal tubular epithelial cells in DM group were significantly higher than those in N group (P <0.01). The expression of α-SMA and TGF-β1 in DM group were significantly increased by 3.4-fold and 1.1-fold compared with that in N group (P <0.01) α-SMA, TGF-β1 expression decreased by 55% and 40% respectively compared with DM group. Conclusion MMF can down-regulate the expression of α-SMA and TGF-β1 in renal tubular epithelial cells and inhibit the renal tubular epithelial cell transdifferentiation, which can protect the kidney.