霉酚酸酯对糖尿病大鼠肾小管上皮细胞转分化的影响

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

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 and possible mechanism of mycophenolate mofetil （MMF） on renal tu- bular 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 orotein, serum creatinine and tubulo-interstitial damage index （TⅡ） （P 〈 0.01 ）. All the oarameters 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 ceils were higher in group DM compared with group N（ P 〈0.01 ）. But expressions of α-SMA and TGF-β1 in group M were sig- nificantly 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 pro- tective role in diabetic nephropathy.