二甲双胍对2型糖尿病模型大鼠肾组织巨噬细胞移动抑制因子及其受体CD74表达的影响

Effects of metformin on MIF/CD74 expression of renal tissues in type 2 diabetic rats

目的观察二甲双胍(MET)对2型糖尿病(T2DM)模型大鼠肾组织巨噬细胞移动抑制因子(MIF)及其受体CD74、肾小球足细胞表面标志蛋白podocalyxin(PCX)表达及尿蛋白排泄的影响,探讨MET对糖尿病肾病的可能保护机制。方法 44只雄性SD大鼠随机选择10只作为正常对照组(NC组),余下大鼠采用高脂饮食+小剂量链脲佐菌素30 mg/kg腹腔注射诱导T2DM大鼠模型。30只T2DM模型大鼠随机分为3组,分别给予MET (MET组)、格列本脲(GLY组)、0.9%氯化纳溶液(DM组)灌胃。灌胃8周后观察各组大鼠血液中血糖(FBG)、糖化血红蛋白(HbA1c)、尿素氮(BUN),尿液中白蛋白/肌酐(UACR)、MIF/肌酐(UMCR)、CD74/肌酐(UCCR)、PCX/肌酐(UPCR)以及肾组织MIF、CD74、PCX mRNA及蛋白表达的变化。结果 8周末时,获得相应检测值:(1)与DM组比较,MET组及GLY组FBG、HbA1c、BUN、UACR、UMCR、UCCR、UPCR、肾组织MIF、CD74的mRNA和蛋白表达降低,但高于NC组,差异有统计学意义(P<0.05);肾组织PCX表达升高,但低于NC组,差异有统计学意义(P<0.05)。(2)与GLY组比较,MET组UACR、UMCR、UCCR和UPCR,肾组织MIF、CD74 mRNA和蛋白表达降低,PCX表达升高,且差异有统计学意义(P<0.05);两组间FBG和HbA1c水平差异无统计学意义。结论 MET对大鼠肾脏具有保护作用,该作用可能与其抑制MIF-CD74轴介导的炎症级联反应有关。

Objective To observe the effects of metformin(MET) on the MIF,CD74 and podocalyxin(PCX) expression in renal tissues of type 2 diabetic mellitus(T2 DM) rats,and explore its possible renoprotective mechanisms. Methods 10 SD rats served as normal control group(NC,n=10), 30 type 2 diabetes SD rats induced by high fat diet and streptozotocin were randomly divided into DM group, MET group and glibenclamide(GLY) group. 8 weeks later, fasting blood glucose(FBG), hemoglobin A1 c(HbA1 c),blood urea nitrogen(BUN), urine albumin/creatinine(UACR), MIF/creatinine(UMCR), CD74/creatinine(UCCR), PCX/creatinine(UPCR), and MIF,CD74, PCX mRNA and relative protein expression in renal tissue were measured. Results(1) The FBG, HbA1 c, BUN, UACR, UMCR, UCCR, UPCR and the mRNA and protein expression of MIF and CD74 in renal tissue in MET group and GLY group were significantly lower than those in DM group,but higher than those in NC group(P<0.05). The expression of PCX in renal tissue was significantly higher than that in DM group, which was lower than that in NC group(P<0.05).(2) Compared with GLY group, UACR, UMCR, UCCR,UPCR and the expression of MIF and CD74 mRNA and protein in renal tissue in MET group decreased significantly, and the expression of PCX was significantly increased. There was no significant difference in FBG and HbA1 c levels between two groups.Conclusion MET exerts a reno-protective effect of type 2 diabetic rats, which may be related to its inhibition of the MIF-CD74 axis-mediated inflammatory cascade.