摘要
目的 观察螺内酯对1型糖尿病大鼠足细胞黏附作用的影响.方法 选取SPF级健康雄性Wistar大鼠16只(6～7周龄,体质量180～220 g),尾静脉注射链脲佐菌素建立1型糖尿病大鼠模型.成模大鼠(n=13)以简单随机化方法分为模型对照组(n=7)和螺内酯治疗组(n=6),另设正常对照组(n=6).螺内酯治疗组以40 mg·kg^(-1)·d^(-1)螺内酯灌胃,正常对照组和模型对照组以剂量相当的蒸馏水灌胃.12周后观察大鼠空腹血糖、收缩压、24 h尿白蛋白定量等指标;采用免疫组织化学法、Western blot技术观察肾小球整合素α3表达情况.组间均数比较采用方差分析,其中两两比较采用q检验.结果 干预前,模型对照组大鼠空腹血糖水平明显高于正常对照组[分别为(23.96±3.86)和(4.85±0.50)mmol/L,q=12.00,P＜0.01],模型对照组和螺内酯治疗组间空腹血糖水平差异无统计学意义[分别为(23.96±3.86)和(22.76±3.85)mmol/L,q=0.95,P＞0.05].正常对照组、模型对照组、螺内酯治疗组间收缩压差异无统计学意义(F=0.51,P＞0.05).12周后,模型对照组大鼠空腹血糖水平明显高于正常对照组[分别为(28.54±2.24)和(5.20±0.19)mmol/L,q=54.39,P＜0.01];三组间收缩压差异无统计学意义(F=0.18,P＞0.05);模型对照组大鼠24 h尿白蛋白较正常对照组明显增加[分别为(6.54±1.14)和(1.01±0.08)mg/d,q=19.50,P＜0.01],整合素α3蛋白表达明显减少(分别为0.28±0.62和0.89±0.07,q=24.33,P＜0.05);螺内酯治疗组和模型对照组空腹血糖水平差异无统计学意义(q=2.73,P＞0.05),螺内酯治疗组较模型对照组24 h尿白蛋白排泄明显减少[分别为(5.32±0.31)和(6.54±1.14)mg/d,q=4.30,P＜0.05],整合素α3蛋白表达明显增加(分别为0.48±0.62和0.28±0.62,q=8.11,P＜0.01).结论 螺内酯可在不影响空腹血糖和血压水平的情况下减少1型糖尿病大鼠尿液中白蛋白和足细胞的排泄,上调肾小球整合素α3的表达,起到保护足细胞黏附功能的作用,这可能是螺内酯对糖尿病肾病的保护机制之一.
Objective To investigate the effects of spironolactone on podocytic adhesive capacity in type 1 diabetic rats.Methods Sixteen healthy male Wistar rats(180 to 220 g,6 to 7 weeks old)were injected with STZ via a tail vein to induce type 1 diabetes,and 13 of them were randomly divided into the spironolactone treatment group(40 mg·kg^(-1)·d^(-1) spironolactone gavage for 12 weeks,n=6)or the diabetic control group(distilled water alone,n=7).Another 6 body-weight-matched rats were served as the normal control group.On week 12,24-hour urinary albumin,systolic blood pressure(SBP),and fasting blood glucose(FBG)were evaluated.Expression of integrin α3 was detected by immunohistochemistry and Western blot.One-way ANOVA with the Students-Newman-Keuls test as a post hoc test was used to evaluate significant differences between the groups.Results Before the administration of spironolactone,FBG of the diabetic control group was significantly higher than that of the normal control group((23.96±3.86)and (4.85±0.50)mmol/L,respectively;q=12.00,P ＜ 0.01);however,there was no significant difference between the diabetic group and the spironolactone treatment group((23.96±3.86)and(22.76±3.85)mmol/L,respectively;q=0.95,P ＞ 0.05).SBP did not differ significantly between the three groups(F=0.51,P ＞0.05).At 12 weeks,rats received STZ alone revealed an increase in FBG((28.54±2.24)and (5.20±0.19)mmol/L,respectively;q=54.39,P ＜0.01),which was not influenced by the treatment with spironolactone(q=2.73,P ＞ 0.05).SBP did not differ significantly between the three groups(F=0.18,P ＞ 0.05).Furthermore,24-hour urinary albumin was significantly increased in the diabetic control group ((6.54±1.14)and(1.01±0.08)mg/d,respectively;q=19.50,P ＜ 0.01).In contrast,the spironolactone treatment group showed considerable improvement in urine albumin((5.32±0.31)and (6.54±1.14)mg/d,respectively;q=4.30,P ＜ 0.05),as well as up-regulation of integrin a3 protein expression(0.48±0.62 and 0.28±0.62,respectively;q=8.11,P ＜0.01).Conclusion After the administration of spironolactone,the expression of integrin or3 was significantly increased in STZ-induced type 1 diabetic rats without affecting FBG and SBP,suggesting that beneficial effects of spironolactone on podocytic adhesion may be one of its protective mechanisms against diabetic nephropathy.
出处
《中华糖尿病杂志》
CAS
2009年第4期-,共6页
CHINESE JOURNAL OF DIABETES MELLITUS
基金
天津市卫生局科技基金项目
