中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2009年
4期
291-296
,共6页
螺内酯%糖尿病,1型%足细胞%整合素
螺內酯%糖尿病,1型%足細胞%整閤素
라내지%당뇨병,1형%족세포%정합소
Spironolactone%Type 1 diabetes mellitus%Podocytes%Integrin
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.
目的 觀察螺內酯對1型糖尿病大鼠足細胞黏附作用的影響.方法 選取SPF級健康雄性Wistar大鼠16隻(6～7週齡,體質量180～220 g),尾靜脈註射鏈脲佐菌素建立1型糖尿病大鼠模型.成模大鼠(n=13)以簡單隨機化方法分為模型對照組(n=7)和螺內酯治療組(n=6),另設正常對照組(n=6).螺內酯治療組以40 mg·kg~(-1)·d~(-1)螺內酯灌胃,正常對照組和模型對照組以劑量相噹的蒸餾水灌胃.12週後觀察大鼠空腹血糖、收縮壓、24 h尿白蛋白定量等指標;採用免疫組織化學法、Western blot技術觀察腎小毬整閤素α3錶達情況.組間均數比較採用方差分析,其中兩兩比較採用q檢驗.結果 榦預前,模型對照組大鼠空腹血糖水平明顯高于正常對照組[分彆為(23.96±3.86)和(4.85±0.50)mmol/L,q=12.00,P＜0.01],模型對照組和螺內酯治療組間空腹血糖水平差異無統計學意義[分彆為(23.96±3.86)和(22.76±3.85)mmol/L,q=0.95,P＞0.05].正常對照組、模型對照組、螺內酯治療組間收縮壓差異無統計學意義(F=0.51,P＞0.05).12週後,模型對照組大鼠空腹血糖水平明顯高于正常對照組[分彆為(28.54±2.24)和(5.20±0.19)mmol/L,q=54.39,P＜0.01];三組間收縮壓差異無統計學意義(F=0.18,P＞0.05);模型對照組大鼠24 h尿白蛋白較正常對照組明顯增加[分彆為(6.54±1.14)和(1.01±0.08)mg/d,q=19.50,P＜0.01],整閤素α3蛋白錶達明顯減少(分彆為0.28±0.62和0.89±0.07,q=24.33,P＜0.05);螺內酯治療組和模型對照組空腹血糖水平差異無統計學意義(q=2.73,P＞0.05),螺內酯治療組較模型對照組24 h尿白蛋白排洩明顯減少[分彆為(5.32±0.31)和(6.54±1.14)mg/d,q=4.30,P＜0.05],整閤素α3蛋白錶達明顯增加(分彆為0.48±0.62和0.28±0.62,q=8.11,P＜0.01).結論 螺內酯可在不影響空腹血糖和血壓水平的情況下減少1型糖尿病大鼠尿液中白蛋白和足細胞的排洩,上調腎小毬整閤素α3的錶達,起到保護足細胞黏附功能的作用,這可能是螺內酯對糖尿病腎病的保護機製之一.
목적 관찰라내지대1형당뇨병대서족세포점부작용적영향.방법 선취SPF급건강웅성Wistar대서16지(6～7주령,체질량180～220 g),미정맥주사련뇨좌균소건립1형당뇨병대서모형.성모대서(n=13)이간단수궤화방법분위모형대조조(n=7)화라내지치료조(n=6),령설정상대조조(n=6).라내지치료조이40 mg·kg~(-1)·d~(-1)라내지관위,정상대조조화모형대조조이제량상당적증류수관위.12주후관찰대서공복혈당、수축압、24 h뇨백단백정량등지표;채용면역조직화학법、Western blot기술관찰신소구정합소α3표체정황.조간균수비교채용방차분석,기중량량비교채용q검험.결과 간예전,모형대조조대서공복혈당수평명현고우정상대조조[분별위(23.96±3.86)화(4.85±0.50)mmol/L,q=12.00,P＜0.01],모형대조조화라내지치료조간공복혈당수평차이무통계학의의[분별위(23.96±3.86)화(22.76±3.85)mmol/L,q=0.95,P＞0.05].정상대조조、모형대조조、라내지치료조간수축압차이무통계학의의(F=0.51,P＞0.05).12주후,모형대조조대서공복혈당수평명현고우정상대조조[분별위(28.54±2.24)화(5.20±0.19)mmol/L,q=54.39,P＜0.01];삼조간수축압차이무통계학의의(F=0.18,P＞0.05);모형대조조대서24 h뇨백단백교정상대조조명현증가[분별위(6.54±1.14)화(1.01±0.08)mg/d,q=19.50,P＜0.01],정합소α3단백표체명현감소(분별위0.28±0.62화0.89±0.07,q=24.33,P＜0.05);라내지치료조화모형대조조공복혈당수평차이무통계학의의(q=2.73,P＞0.05),라내지치료조교모형대조조24 h뇨백단백배설명현감소[분별위(5.32±0.31)화(6.54±1.14)mg/d,q=4.30,P＜0.05],정합소α3단백표체명현증가(분별위0.48±0.62화0.28±0.62,q=8.11,P＜0.01).결론 라내지가재불영향공복혈당화혈압수평적정황하감소1형당뇨병대서뇨액중백단백화족세포적배설,상조신소구정합소α3적표체,기도보호족세포점부공능적작용,저가능시라내지대당뇨병신병적보호궤제지일.
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.
