霉酚酸酯对2型糖尿病大鼠肾脏结构和功能的影响

Effect of mycophenolate mofetil on kidney structures and functions of type 2 diabetic rats

目的观察霉酚酸酯对2型糖尿病大鼠肾脏的保护作用并探讨其机制。方法将清洁级Wistar雌性大鼠36只随机分为正常对照组、糖尿病组和霉酚酸酯治疗组。霉酚酸酯治疗组给予霉酚酸酯15 mg.kg-1.d-1灌胃治疗。13周后检测各组大鼠血糖,血脂,血胰岛素,尿白蛋白排泄率,内生肌酐清除率;HE及PAS染色观察肾脏病理改变;用免疫组化方法检测肾组织中结缔组织生长因子（CTGF）、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶抑制剂-1（TIMP-1）和单核细胞趋化蛋白-1（MCP-1）的表达。结果与正常对照组比较,糖尿病组大鼠血糖,血脂,24 h尿白蛋白排泄率,内生肌酐清除率均明显升高（P〈0.05）;其肾重、肾重/体重、肾小球面积、肾小球体积、细胞外基质相对面积亦明显升高（P〈0.05）;肾脏组织中CTGF、TIMP-1和MCP-1的表达增强（P〈0.05）,而MMP-9表达则下降。霉酚酸酯治疗组大鼠上述各项指标均较糖尿病组好转（P〈0.05）。结论霉酚酸酯对2型糖尿病大鼠肾脏有部分保护作用,其机制可能部分是通过下调2型糖尿病大鼠肾脏CTGF和MCP-1的表达,调节MMP-9和TIMP-1的平衡来实现的。

Objective To investigate the renal protection effect and mechanism of mycophenolate mofetil in type 2 diabetic rats. Methods Forty eight Wistar rats （female, 160 - 180g body weight） were divided into three groups： normal control group, diabetic rats group, diabetic rats treated with mycophenolate mofetil group（ MMF, 15 mg·kg^-1·d^1 ）. Blood glucose, blood insulin, blood lipid, urinary albumin excretory rate and creatinine clearance rate were measured after 13 weeks. Kidney pathology changes were observed with HE and PAS staining. Immunohistechemistry was used to analyze the expression of CTGF, MMP-9, TIMP-1 and MCP-1. Results No significant differences of blood glucose and blood insulin were found between diabetic rats group and mycophenolate mofetil treatment group. Compared with the untreated diabetic group, urinary albumin excretion rate and creatinine clearance rate of MMF treated rats group were decreased significantly. The expression of CTGF, TIMP-1 and MCP-1 in MMF group were much lower than that in diabetic untreated group, while the expression of MMP-9 was up - regulated. MMF also meliorated the histological changes of diabetic rats. Conclusion Mycophenolate mofetil has some renal protective effect on type 2 diabetic rats, the mechanism may be through down - regulating the expression of CTGF and MCP- 1, regulating the balance of between MMP-9 and TIMP-1, and reducing monocyte/macrophage infitration.