CAJ | 학술논문

目的观察不同剂量二甲双胍( MET)对2型糖尿病(T2DM)模型大鼠肾组织nephrin 表达的影响,了解其对肾小球足细胞的保护作用. 方法高脂饲料喂养结合腹腔注射小剂量链脲佐菌素(STZ)建立T2DM大鼠模型,给予不同剂量[150、300、500 mg/(kg·d)]MET干预治疗(MET1组、MET2组、MET3组),并设立糖尿病模型组(T2DM组)和正常对照组(NC组). 8 周后,观察各组大鼠血糖(BG)、糖化血红蛋白(HbA1c)、尿素氮(BUN)、尿白蛋白和尿nephrin排泄的情况以及肾脏组织病理改变和nephrin表达的变化. 结果 8 周末, MET 三组 BG、HbA1c、尿白蛋白/尿肌酐(UACR)、基底膜厚度(GBMT)和足突融合率(FRFP)明显低于T2DM 组,高于 NC 组(P <0. 05);MET2、MET3 组低于MET1 组( P <0. 05 ). MET 组血 BUN、尿 nephrin/尿肌酐(UNER)低于T2DM组(P<0. 05),MET3与MET1组差异有统计学意义(P<0. 05). MET组肾组织nephrin蛋白和mR-NA表达较T2DM 组显著升高(P<0. 05),但是低于 NC组( P<0. 05 );各MET组间nephrin蛋白表达差异无统计学意义,MET3 组nephrin mRNA表达高于MET1 组( P<0. 05 ).结论 MET可减轻T2DM模型大鼠肾组织nephrin表达的减少和保护足细胞,并有一定的剂量依赖性.
목적 관찰불동제량이갑쌍고( MET)대2형당뇨병(T2DM)모형대서신조직nephrin 표체적영향,료해기대신소구족세포적보호작용. 방법 고지사료위양결합복강주사소제량련뇨좌균소(STZ)건립T2DM대서모형,급여불동제량[150、300、500 mg/(kg·d)]MET간예치료(MET1조、MET2조、MET3조),병설립당뇨병모형조(T2DM조)화정상대조조(NC조). 8 주후,관찰각조대서혈당(BG)、당화혈홍단백(HbA1c)、뇨소담(BUN)、뇨백단백화뇨nephrin배설적정황이급신장조직병리개변화nephrin표체적변화. 결과 8 주말, MET 삼조 BG、HbA1c、뇨백단백/뇨기항(UACR)、기저막후도(GBMT)화족돌융합솔(FRFP)명현저우T2DM 조,고우 NC 조(P <0. 05);MET2、MET3 조저우MET1 조( P <0. 05 ). MET 조혈 BUN、뇨 nephrin/뇨기항(UNER)저우T2DM조(P<0. 05),MET3여MET1조차이유통계학의의(P<0. 05). MET조신조직nephrin단백화mR-NA표체교T2DM 조현저승고(P<0. 05),단시저우 NC조( P<0. 05 );각MET조간nephrin단백표체차이무통계학의의,MET3 조nephrin mRNA표체고우MET1 조( P<0. 05 ).결론 MET가감경T2DM모형대서신조직nephrin표체적감소화보호족세포,병유일정적제량의뢰성.
Objective To observe the effects of different doses of metformin( MET) on the expression of renal tis-sue nephrin protein and mRNA in type 2 diabetes mellitus(T2DM) model rats and understand its protective effect on glomerular podocytes. Methods The model rats of T2DM were established by being fed with high fat-diet and intraperitoneal injection of low dose of streptozotocin ( STZ) . Diabetic rats were divided into different dose metform-in groups (group MET1,group MET2 and group MET3, 150,300, 500 mg/(kg·d), respectively),T2DM model group (T2DM group) and normal control group (NC group) were also set up. After 8 weeks,blood glucose (BG), glycated hemoglobin (HbA1c), urinary albumin/urine creatinine (UACR),urinary nephrin excretion,renal tissue pathological changed and nephrin expression were detected. Results The levels of BG, HbA1c,UACR,glomerular basement membrane thickness (GBMT) and food process fusion ratio (FRFP) in MET groups were significantly lower than those of T2DM group, while higher than those of NC group (P <0. 05), and those above in MET2, MET3 were lower significantly compared with MET1 group(P<0. 05);the levels of blood BUN and urinary neph-rin/urine creatinine (UNER) in MET groups were lower than those of T2DM group (P<0. 05), there was statisti-cally significant difference between MET3 and MET1 group ( P<0. 05 );the expression of renal tissue nephrin pro-tein and mRNA in MET groups were significantly increased compared with that of T2 DM group ( P<0. 05 ) , but lower than that of NC group ( P<0. 05 );the expression of nephrin protein had no statistically significant difference among MET groups, while the expression of nephrin mRNA in MET3 group was higher than that of MET1 group ( P<0. 05 ) . Conclusion MET can alleviate the down-regulation of renal tissue nephrin expression and provide some protection against glomerular podocyte damage in T2DM rats with a dose-dependent manner.