国际内分泌代谢杂志
國際內分泌代謝雜誌
국제내분비대사잡지
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2011年
3期
148-151
,共4页
常宝成%杨菊红%任慧珠%王颖%单春艳%郑妙艳%陈莉明%方佩华
常寶成%楊菊紅%任慧珠%王穎%單春豔%鄭妙豔%陳莉明%方珮華
상보성%양국홍%임혜주%왕영%단춘염%정묘염%진리명%방패화
阿托伐他汀%普伐他汀%胰岛素含量%胰岛素mRNA
阿託伐他汀%普伐他汀%胰島素含量%胰島素mRNA
아탁벌타정%보벌타정%이도소함량%이도소mRNA
Atorvastatin%Pravastatin%Insulin content%Insulin mRNA
目的 观察阿托伐他汀、普伐他汀对大鼠胰岛β细胞胰岛素合成的影响及机制.方法 实验分对照组、阿托伐他汀组和普伐他汀组,胆管注射胶原酶法分离大鼠胰岛,放射免疫法测定阿托伐他汀、普伐他汀作用24 h后胰岛素的含量,定鼍PCR分析阿托伐他汀、普伐他汀作用24 h后对β细胞胰岛素mRNA表达的影响;构建人胰岛素启动子-荧光素酶质粒,脂质体转染MIN6细胞,双荧光素酶法观察100 μmol/L阿托伐他汀、普伐他汀作用24 h、48 h后对胰岛素启动子活性的影响;3组间比较采用方差分析.结果 与对照组相比,100 μmol/L阿托伐他汀作用24 h,胰岛β细胞胰岛素含量被抑制到对照组的76.3%(P<0.05),胰岛素mRNA的表达[(0.125 232 ±0.014 827)vs.(0.264 896±0.029 541),P<0.05]和荧光素酶活性[(0.763 616±0.253 780)vs.(1.290 601±0.386 566),P<0.05]均受到明显抑制;普伐他汀未见上述抑制作用.结论 高浓度阿托伐他汀通过抑制大鼠胰岛β细胞胰岛素mRNA表达而抑制胰岛素合成,抑制效应与其对胰岛素启动子活性的抑制有关,抑制程度与其脂溶性强弱有关.
目的 觀察阿託伐他汀、普伐他汀對大鼠胰島β細胞胰島素閤成的影響及機製.方法 實驗分對照組、阿託伐他汀組和普伐他汀組,膽管註射膠原酶法分離大鼠胰島,放射免疫法測定阿託伐他汀、普伐他汀作用24 h後胰島素的含量,定鼉PCR分析阿託伐他汀、普伐他汀作用24 h後對β細胞胰島素mRNA錶達的影響;構建人胰島素啟動子-熒光素酶質粒,脂質體轉染MIN6細胞,雙熒光素酶法觀察100 μmol/L阿託伐他汀、普伐他汀作用24 h、48 h後對胰島素啟動子活性的影響;3組間比較採用方差分析.結果 與對照組相比,100 μmol/L阿託伐他汀作用24 h,胰島β細胞胰島素含量被抑製到對照組的76.3%(P<0.05),胰島素mRNA的錶達[(0.125 232 ±0.014 827)vs.(0.264 896±0.029 541),P<0.05]和熒光素酶活性[(0.763 616±0.253 780)vs.(1.290 601±0.386 566),P<0.05]均受到明顯抑製;普伐他汀未見上述抑製作用.結論 高濃度阿託伐他汀通過抑製大鼠胰島β細胞胰島素mRNA錶達而抑製胰島素閤成,抑製效應與其對胰島素啟動子活性的抑製有關,抑製程度與其脂溶性彊弱有關.
목적 관찰아탁벌타정、보벌타정대대서이도β세포이도소합성적영향급궤제.방법 실험분대조조、아탁벌타정조화보벌타정조,담관주사효원매법분리대서이도,방사면역법측정아탁벌타정、보벌타정작용24 h후이도소적함량,정타PCR분석아탁벌타정、보벌타정작용24 h후대β세포이도소mRNA표체적영향;구건인이도소계동자-형광소매질립,지질체전염MIN6세포,쌍형광소매법관찰100 μmol/L아탁벌타정、보벌타정작용24 h、48 h후대이도소계동자활성적영향;3조간비교채용방차분석.결과 여대조조상비,100 μmol/L아탁벌타정작용24 h,이도β세포이도소함량피억제도대조조적76.3%(P<0.05),이도소mRNA적표체[(0.125 232 ±0.014 827)vs.(0.264 896±0.029 541),P<0.05]화형광소매활성[(0.763 616±0.253 780)vs.(1.290 601±0.386 566),P<0.05]균수도명현억제;보벌타정미견상술억제작용.결론 고농도아탁벌타정통과억제대서이도β세포이도소mRNA표체이억제이도소합성,억제효응여기대이도소계동자활성적억제유관,억제정도여기지용성강약유관.
Objective To evaluate the effect of atorvastatin and pravastatin on insulin synthesis from islet β cell in rat and its mechanisms.Methods In the experiment,it was divided into control group,atorvastatin group and pravastatin group.Pancreatic islets were isolated by the collagenase method.Cultured with 100 μmol/L atorvastatin or pravastatin for 24 hours respectively,the alteration of insulin content was measnred by RIA,and the expression of insulin mRNA from rats'islet β cells was accessed by quantitative PCR.The human insulin promoter-luciferase vector was constructed and transfected to MIN6 cells by using Lipofectamine 2000.Cultured with 100 μmol/L atorvastatin or pravastatin for 24 and 48 hours respectively,the activity of lnciferase was measured by the dual-luciferase reporter assay system to evaluate the activity of insulin promoter.Difference between the three groups was determined by one-way analysis of variance.Results Cultured with 100 μmol/L atorvastatin for 24 hours,the insulin content was significantly decreased to 76.3%of the control group(P<0.05),the mRNA expression levels[(0.125 232 ±0.014 827)vs.(0.264 896±0.029 541),P<0.05]and the activity of luciferase[(0.763 616±0.253 780)vs.(1.290 601±0.386 566),P<0.05]were all significantly inhibited compared with the control group,but the inhibitory effects were not shown in the pravastatin group.Conclusion In a higher concentration,atorvastatin may reduce the synthesis of insulin by inhibiting the expression of insulin mRNA of islet β cells.This effect is relative to its inhibition on the activity of insulin promoter,and the degree of inhibition is relative to its lipophilicity.
