霉酚酸酯对糖尿病肾病大鼠肾小球硬化的研究

Study of mycophenolate mofetil on glomerulosclerosis in rats with diabetic nephropathy

目的通过霉酚酸酯对链脲佐菌素（STZ）糖尿病肾病大鼠模型的干预治疗，探讨其对肾组织转化生长因子β1（TGF-β1）及血浆内皮素（ETI）的影响。方法采用STZ腹腔注射法建立糖尿病肾病动物模型，将60只Wistar大鼠随机分为正常对照组（A组）、糖尿病肾病组（B组）及霉酚酸酯治疗组（C组），每组各20只。C组给予霉酚酸酯（15mg·kg^-1·d^-1）灌胃治疗，12周后检测各组大鼠24h尿白蛋白、肌酐清除率（Ccr）、血糖、血ET-1浓度、HE和PAS染色观察肾脏病理改变、免疫组化方法检测TGF-β1的表达。结果霉酚酸酯能降低糖尿病肾病大鼠的24h尿蛋白定量、血ET-1、TGF-β1的表达；升高Ccr；减轻肾组织系膜细胞、系膜基质增生，减轻基底膜肥厚，肾小球硬化明显减少。结论霉酚酸酯对糖尿病大鼠肾脏有保护作用，其机制可能与减少蛋白尿，降低血ET-1、TGF-β1的表达有关。

Objective To investigate the effects of mycophenolate mofetil on renal expression of transforming growth factor-β1 and endothelin -1 in streptozotocin（STZ） induced diabetic rats. Method Animal model of diabetes was established by intraperitoneal injection of STZ. Sixty Wistar rats were divided into three groups： normal control rats, diabetic rats, and diabetic rats treated with mycophenolate mofetil （MMF, 15 mg/kg/d）. 12weeks later, 24 h urinary albumin excretion, creatinine clearance （Ccr）, blood glucose,ET-1 ,TGF-β1 were measured, and kidney pathology was observed. Results Mycophenolate mofetil decreased 24h urinary albumin,TGF-β1 ,ET-1 and inceased Ccr. Proliferation of renal mesangial ceils was alleviated, hypertrophy of basement menbrane was decreased. Conclusions Mycophenolatemofetil has renal protective effect on diabetic rats. Its mechanism may be related to the decrease of 24h urinary albumin, as wellas TGF-β1 , ET-1 expression.