CAJ | 학술논문

目的：观察不同剂量二甲双胍（M E T ）对高脂饮食联合低剂量链脲佐菌素诱导的2型糖尿病大鼠肾组织足细胞podocalyxin（PCX）表达的影响。方法选择SD大鼠48只，随机分为对照组（8只）、模型组（9只）、格列本脲组（8只），低剂量M ET组（8只）、中剂量M ET组（8只）和高剂量M ET组（7只）。8周末测尿白蛋白、PCX和肌酐，并计算尿白蛋白／肌酐（UACR）、尿 PCX／肌酐（UPCR）。取血测空腹血糖、糖化血红蛋白（HbA1c）、尿素、TG和LDL‐C。留取肾组织做免疫组织化学及实时PCR检测PCX蛋白和mRNA表达，电镜观察肾组织病理改变。结果与对照组比较，模型组大鼠空腹血糖、HbA1c、尿素、TG、LDL‐C、UACR、UPCR、基底膜厚度（GBMT）和足突融合率（FRFP）明显增加，而肾组织PCX蛋白和mRNA表达明显减少（P＜0．05）。与模型组比较，不同剂量MET 组尿素、TG、LDL‐C、GBMT、FRFP、UACR和UPCR水平明显减低，肾组织PCX蛋白和mRNA表达呈剂量依赖性的增加（P＜0．05）。与格列本脲组比较，不同剂量MET组血尿素、TG、LDL‐C、GBMT、FRFP、UACR和UPCR水平明显减低，肾组织PCX蛋白和mRNA表达增加（P＜0．05）。结论 MET可以通过调节2型糖尿病模型大鼠肾组织PCX的表达，发挥降糖以外的肾组织足细胞保护作用，且作用具有一定的剂量依赖性。
목적：관찰불동제량이갑쌍고（M E T ）대고지음식연합저제량련뇨좌균소유도적2형당뇨병대서신조직족세포podocalyxin（PCX）표체적영향。방법선택SD대서48지，수궤분위대조조（8지）、모형조（9지）、격렬본뇨조（8지），저제량M ET조（8지）、중제량M ET조（8지）화고제량M ET조（7지）。8주말측뇨백단백、PCX화기항，병계산뇨백단백／기항（UACR）、뇨 PCX／기항（UPCR）。취혈측공복혈당、당화혈홍단백（HbA1c）、뇨소、TG화LDL‐C。류취신조직주면역조직화학급실시PCR검측PCX단백화mRNA표체，전경관찰신조직병리개변。결과여대조조비교，모형조대서공복혈당、HbA1c、뇨소、TG、LDL‐C、UACR、UPCR、기저막후도（GBMT）화족돌융합솔（FRFP）명현증가，이신조직PCX단백화mRNA표체명현감소（P＜0．05）。여모형조비교，불동제량MET 조뇨소、TG、LDL‐C、GBMT、FRFP、UACR화UPCR수평명현감저，신조직PCX단백화mRNA표체정제량의뢰성적증가（P＜0．05）。여격렬본뇨조비교，불동제량MET조혈뇨소、TG、LDL‐C、GBMT、FRFP、UACR화UPCR수평명현감저，신조직PCX단백화mRNA표체증가（P＜0．05）。결론 MET가이통과조절2형당뇨병모형대서신조직PCX적표체，발휘강당이외적신조직족세포보호작용，차작용구유일정적제량의뢰성。
Objective To study the effect of metformin (MET)on expression of podocalyxin (PCX) in renal tissue of type 2 diabetes mellitus rats .Methods Forty eight SD rats were divided into control group (n=8) ,model group (n=9) ,glyburide group (n=8) ,low M ET dose group (n=8) , moderate MET dose group(n=8)and high MET dose group (n=7) .Urinary albumin (UA) ,PCX and creatinine (CR) ,and UA/CR ratio (UACR) ,UPCX/CR ratio (UPCR) were assayed at the end of 8 weeks .Serum levels of FPG ,HbA1c ,urea ,TG and LDL‐C were measured .PCX protein and mRNA expression was detected by immunohistochemistry and RT‐PCR respectively .Renal tissue lesions were observed under electron microscope .Results The levels of FPG ,HbA1c ,ure‐a ,TG ,LDL‐C ,and UACR ,UPCR ,basement membrane thickness (GBMT)and foot process fusion rate (FRFP) were significantly higher while the expression level of PCX protein and mRNA was significantly lower in model group than in control group (P< 0 .05) .The levels of urea ,TG , LDL‐C ,and GBMT ,FRFP ,UACR ,UPCR were significantly lower while the expression level of PCX protein and mRNA was significantly higher in three MET dose groups than in model group and glyburide group (P<0 .05) .Conclusion MET protects renal podocytes by regulating PCX expression in renal tissue of type 2 diabetes mellitus rats in a dose‐dependent manner .