【摘要】 目的观察二甲双胍对糖尿病模型大鼠肾组织结缔组织生长因子(CTGF)表达的影响,探讨其对肾脏保护的机制。方法 35只SD大鼠随机分为正常对照组(NC,n=9)、糖尿病组(T2DM,n=10)、格列本脲组(GLY,n=8)和二甲双胍治疗组(MET,n=8)。T2DM、GLY和MET组采用高脂饮食联合小剂量STZ腹腔注射建立T2DM大鼠模型,建模成功后,GLY和MET组予药物干预8周。检测各组FPG、HbA1c,FIns、BUN、UAlb及尿肌酐(Ucr)水平;电镜观察肾小球基底膜厚度(GBMT)、足细胞融合率(FRFP);免疫组织化学法和RT‐PCR检测肾组织中CTGF蛋白[表示为图像中的阳性反应区累积光密度(IOD),记为CTGFIOD]和mRNA(记为CTGFmRNA)表达;ELISA检测尿CTGF蛋白排泄情况。结果与NC组比较,T2DM组FPG、UACR、尿CTGF/Ucr(UCTR)、GBMT、CTGFIOD和CTGFmRNA表达水平明显升高[(4. 45±1. 07)vs(15. 60±1. 56)mmol/L,(34. 09±2. 92)vs(136. 31±6. 84)mg/g,(822. 41±116. 84)vs(4386. 80±164. 3)pg/g,(106. 00±10. 23)vs(266. 58±21. 68)nm,(19. 24±6. 71)vs(74. 52±15. 45),(1. 02±0. 27)vs(4. 73±0. 77),P<0. 05]。与T2DM组比较,MET组FPG、UACR、UCTR、GBMT、CTGFIOD和CTGFmRNA表达水平降低[(15. 60±1. 56)vs(10. 58±1. 03)mmol/L,(136. 31±6. 84)vs(96. 32±2. 85)mg/g,(4386. 80±164. 3)vs(1220. 90±145. 06)pg/g,(266. 58±21. 68)vs(145. 94±16. 10)nm,(74. 52±15. 45)vs(36. 25±8. 93),(4. 73±0. 77)vs(2. 26±0. 47),P<0. 05)];与GLY组比较,MET组UACR、UCTR、GBMT、CTGFIOD和CTGFmRNA水平降低[(110. 10±6. 76)vs(96. 32±2. 85)mg/g,(4197. 10±103. 98)vs(1220. 90±145. 06)pg/g,(203. 67±23. 32)vs(145. 94±16. 10)nm,(63. 78±15. 00)vs(36. 25±8. 93),(4. 47±0. 76)vs(2. 26±0. 47),P<0. 05],FPG和HbA1c比较,差异无统计学意义(P>0. 05)。结论二甲双胍在改善血糖控制的同时,可降低肾组织中CTGF的表达,该作用可能是其提供肾脏疾病保护作用的机制之一。更多还原

【Abstract】 ObjectiveTo observe the effect of metformin on the expression of connective tissue growth factor(CTGF)in renal tissue of diabetic rats and to explore its protective mechanism of kidney.Methods37 SD rats were randomly divided into normal control group(NC group)and model group. A small dose of STZ was injected intraperitoneally with a high-fat diet to establish a type 2 diabetic rat model.After modeling,the rats were randomly divided into diabetes group(T2 DM group),metformin treatment group[MET,500 mg/(kg·d)]and glibenclamide group[GLY,5 mg/(kg·d)]. After 8 weeks of adminis-tration,fasting plasma gluco(sFPG),glycosylated hemoglobin(HbA1 c),fasting insulin(FIns),urinary albu-min(Alb),urinary CTGF and urine creatinine(Ucr)levels were measured in each group. Electron micros-copy was used to observe the glomerular basement membrane thickness(GBMT),the foot process fusion rate(FRFP). Immunohistochemistry and Real-Time PCR were used to detect the expression of CTGF pro-tein[expressed as the cumulative optical density of the positive reaction zone in the image(IOD),recorded as CTGFIOD]and mRNA(recorded as CTGFmRNA)in renal tissue.ResultsCompared with NC group,the level of FPG[(4. 45±1. 07)vs(15. 60±1. 56)mmol/L],urinary albumin/creatinine(UACR)[(34. 09±2. 92)vs(136. 31±6. 84)mg/g],urinary CTGF/creatinine(UCTR)[(822. 41±116. 84)vs(4386. 8±164. 3)pg/g],GBMT[(106±10. 23)vs(266. 58±21. 68)nm]and CTGFmRNA[(1. 02±0. 27)vs(4. 73±0. 77)]in renal tissue were significantly higher in T2 DM group(P<0. 05). Compared with T2 DM group,the level of FPG[(15. 60±1. 56)vs(10. 58±1. 03)mmol/L],UACR[(136. 31±6. 84)vs(96. 32±2. 85)mg/g],UCTR[(4386. 8±164. 3)vs(1220. 9±145. 06)pg/g],GBMT[(266. 58±21. 68)vs(145. 94±16. 10)nm],CTGFIOD[(74. 52±15. 45)vs(36. 25±8. 93)]and CTGFmRNA[(4. 73±0. 77)vs(2. 26±0. 47)]were significantly decreased in MET group(P<0. 05). Compared with GLY group,the lev-els of UACR[(96. 32±2. 85)vs(110. 10±6. 76)mg/g],UCTR[(1220. 9±145. 06)vs(4197. 1±103. 98)pg/g],GBMT[(145. 94±16. 10)vs(203. 67±23. 32)nm],CTGFIOD[(36. 25±8. 93)vs(63. 78±15. 00)]and CTGFmRNA[(2. 26±0. 47)vs(4. 47±0. 76)]in MET group were significantly decreased(P<0. 05),but there was no significant difference in the levels of FPG[(10. 58±1. 03)vs(11. 78±1. 43)mmol/L]and HbA1 c[(8. 24±0. 33)vs(8. 85±1. 07)%](P>0. 05).ConclusionIn addition to improving glycemic control,metformin can reduce the expression of CTGF in renal tissue,which may be one of its re-nal protective mechanisms.更多还原