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目的:探讨可溶性环氧化酶水解酶抑制剂-1471(sEHI-1471)预防2型糖尿病小鼠胰岛β细胞凋亡的作用及其机制。方法:2型糖尿病KKAy小鼠随机分为2组:sEHI-1471组(18只)及对照组(18只),分别饮用含8mg/L的sEHI-1471或等体积生理盐水的饮用水,将同周龄的雄性C57BL/6J小鼠设为正常组,饮水不受干预。比较各组小鼠空腹血糖(FBG)和空腹胰岛素水平(FINS),计算胰岛素抵抗指数(HOMA-IR)。TUNEL检测胰岛β细胞凋亡。Western Blot检测胰腺组织Bcl-2,Bcl-xL,Bim,Bax和Bid表达水平。结果:干预3周后,与正常组相比,对照组FBG、FINS和HOMA-IR指数均显著升高(P<0.05);与对照组相比,sEHI-1471组小鼠FBG、FINS和HOMA-IR指数均显著降低(P<0.05);比较各组凋亡变化的结果,对照组较正常组胰岛β细胞凋亡数显著增加(P<0.05),sEHI-1471组较对照组凋亡细胞数明显下降(P<0.05)。比较各组小鼠胰腺抗凋亡蛋白Bcl-2,Bcl-xL和促凋亡蛋白Bax,Bim,Bid表达水平,对照组相对于正常组Bcl-2,Bcl-xL表达明显降低,Bax,Bim和Bid表达明显升高,而相对于对照组,sEHI-1471组Bax,Bim和Bid表达明显降低,Bcl-2和Bcl-xL表达明显升高(P<0.05)。结论:sEHI-1471能降低血糖,增加糖尿病小鼠对胰岛素的敏感性,减少KKAy小鼠胰岛β细胞凋亡,其机制可能与降低促凋亡蛋白Bax,Bim,Bid表达和增加抗凋亡蛋白Bcl-2和Bcl-xL表达有关。
Objective: To investigate the effect of soluble cyclooxygenase hydrolase inhibitor-1471 (sEHI-1471) on pancreatic β-cell apoptosis in type 2 diabetic mice and its mechanism. Methods: KKAy mice with type 2 diabetes mellitus were randomly divided into 2 groups: sEHI-1471 group (n = 18) and control group (n = 18), drinking drinking water containing 8mg / L sEHI-1471 or equal volume of normal saline Male C57BL / 6J mice of the same age were set as normal group, and drinking water was not interfered. The fasting blood glucose (FBG) and fasting insulin (FINS) were compared between groups to calculate the insulin resistance index (HOMA-IR). TUNEL was used to detect islet β-cell apoptosis. Western Blot detection of pancreatic tissue Bcl-2, Bcl-xL, Bim, Bax and Bid expression levels. Results: Compared with the normal control group, FBG, FINS and HOMA-IR index of the control group were significantly increased after 3 weeks intervention (P <0.05). Compared with the control group, the FBG, FINS and HOMA -IR index decreased significantly (P <0.05). Compared with the results of apoptosis in each group, the apoptosis of pancreatic β-cell in control group was significantly increased (P <0.05), the apoptosis rate in sEHI-1471 group was higher than that in control group The number decreased significantly (P <0.05). The expression of Bcl-2, Bcl-xL and Bax, Bim, Bid in pancreatic tissue of mice in each group were compared. The expression of Bcl-2 and Bcl-2 in Bcl- And Bid expression in sEHI-1471 group were significantly lower than those in control group (P <0.05). Compared with control group, the expression of Bax, Bim and Bid in sEHI-1471 group was significantly decreased and the expression of Bcl-2 and Bcl- CONCLUSION: sEHI-1471 can reduce blood glucose, increase insulin sensitivity in diabetic mice and reduce apoptosis of pancreatic β-cells in KKAy mice. The mechanism may be related to the decrease of Bax, Bim, Bid expression and increase of anti-apoptotic protein Bcl-2 and Bcl-xL expression.