二甲双胍对2型糖尿病模型大鼠肾组织色素上皮衍生因子表达影响的研究

Effects of Metformin on PEDF expression in renal tissues in type 2 diabetic rats

目的观察二甲双胍(MET)对T2DM模型大鼠肾组织色素上皮衍生因子(PEDF)表达的影响,探讨MET对DKD的保护机制。方法高脂饲料喂养结合腹腔注射小剂量STZ建立T2DM大鼠模型并随机分为糖尿病模型(T2DM)组、MET组[MET,300 mg/(kg·d)]和格列本脲(GLY)组[GLY,5 mg/(kg·d)],并设正常对照组(NC)。检测各组FPG、HbA1c,UAlb、尿肌酐(Ucr)、尿PEDF水平和肾小球基底膜厚度(GBMT);免疫组织化学法检测肾组织PEDF蛋白表达,Western blot法检测肾组织PEDF蛋白水平;荧光定量PCR检测肾组织PEDF mRNA表达。结果与NC组比较,T2DM组PEDF的mRNA、蛋白相对表达量降低[(7.11±0.30)vs(0.33±0.03)、(1.07±0.01)vs(0.40±0.01),P<0.05],FPG、HbA1c、UACR、PEDF/Ucr(UPCR)和GBMT升高(P<0.05)。与T2DM组比较,MET组PEDF的mRNA、蛋白相对表达量升高[(0.33±0.03)vs(3.10±0.67)、(0.40±0.01)vs(0.80±0.04),P<0.05],UACR、UPCR和GBMT降低(P<0.05);与GLY组比较,MET组PEDF的mRNA和蛋白相对表达量升高[(1.76±0.67)vs(3.10±0.67)、(0.61±0.15)vs(0.80±0.04),P<0.05],UACR、UPCR、GBMT降低(P<0.05)。结论 MET可增加T2DM大鼠肾组织PEDF表达,降低尿蛋白排泄,改善肾脏病理结构,其机制可能与肾脏保护作用有关。

Objective To observe the effects of Metformin(MET)on the pigment epithelium-derived factor(PEDF)m RNA and protein expression in renal tissues of type 2 diabetes mellitus(T2DM)rats and to explore the protective mechanism of MET on renal damage in diabetic kidney disease(DKD).Methods Type 2 diabetes Sprague-Dawley rats induced by high fat diet and streptozotocin(STZ)were randomly divided into T2DM group,Metformin group[MET,300 mg/(kg·d)],Glibenclamide group[GLY,5 mg/(kg·d)]and the normal control group(NC).FPG,HbA1c,FIns,BUN,urinary albumin(UAlb),urine creatinine(Ucr),urinary PEDF,glomerular basement membrane thickness(GBMT),PEDF mRNA and relative protein expression in renal tissue were measured.Results After 8 weeks,compared with NC group,the levels of PEDF mRNA and relative protein expression[(7.11±0.30)vs(0.33±0.03),(1.07±0.01)vs(0.40±0.01)]decreased significantly in T2DM group(P<0.05);the levels of FPG,HbA1c,UACR,UPCR and GBMT increased significantly in T2DM group(P<0.05).Compared with T2DM group,PEDF mRNA and relative protein level[(0.33±0.03)vs(3.10±0.67),(0.40±0.01)vs(0.80±0.04)]increased significantly in MET group(P<0.05);the levels of UACR,UPCR and GBMT decreased significantly in MET group(P<0.05).Compared with GLY group,the levels of PEDF mRNA and relative protein level[(1.76±0.67)vs(3.10±0.67),(0.61±0.15)vs(0.80±0.04)]increased in MET group;the levels of UACR,UPCR and GBMT decreased in MET group(P<0.05).Conclusion Metformin can up-regulate the expression of PEDF and down-regulate urinary protein excretion in T2DM rat kidney,which may be related to its renal protective mechanism.