霉酚酸酯对糖尿病大鼠肾小管上皮细胞转分化的影响

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。

Effect of mycophenolate mofetil on renal tubular epithelial cells trans-differentiation in diabetic rats

Objective To investigate the effect and possible mechanism of mycophenolate mofetil(MMF) on renal tubular epithelial mesenchymal transition in diabetic rats.Methods Twenty-eight male SD rats were randomly divided into the normal control group(group N,n=8),the diabetes mellitus group(group DM) and diabetes mellitus treated with MMF group(group M,n=10).The diabetes mellitus model was constructed by streptozotocin(STZ) injection.Blood glucose,body weight,kidney weight/body weight,24h urinary protein,serum creatinine and the pathological morphological change of renal tubulo-interstitial damage were detected after 12 weeks.Immunohistochemistrcal staining and Western blot were conducted to detect expressions of α-SMA and TGF-β1 in renal tissues.Results There was a significant difference between group N and group DM in the levels of blood glucose,kidney weight/body weight,24 h urinary protein,serum creatinine and tubulo-interstitial damage index(TII)(P<0.01).All the parameters significantlydecreased in group M compared with group DM(P<0.01),except for the levels of blood glucose and body weight(P>0.05).Immunohistochemical staining showed that expressions of α-SMA and TGF-β1 in renal tubular cells were higher in group DM compared with group N(P<0.01).But expressions of α-SMA and TGF-β1 in group M were significantly lower compared with group DM(P<0.01).Western blot showed that expressions of α-SMA and TGF-β1 in renal tissue of group DM were increased by 3.4 and 1.1 times compared with the group N,and were reduced by 55% and 40% in group M(P<0.01).Conclusion MMF can down-regulate expressions of α-SMA and TGF-β1 in diabetic renal tubular epithelia,prevent the process of epithelial trans-differentiation in diabetic mellitus models,and play a protective role in diabetic nephropathy.