Exenatide对多囊卵巢综合征大鼠胰腺组织SIRT1表达的影响

Expression of SIRT1 mRNA in Pancreas in Rats with Polycystic Ovary Syndrome and Intervention Study of Exenatide

【目的】观察Exenatide对多囊卵巢综合征(PCOS)大鼠胰腺沉默信息调节因子1(SIRT1)表达的影响,探讨其对PCOS大鼠的干预治疗效果及可能机制。【方法】采用脱氢表雄酮(DHEA)诱导建立(n=50)PCOS雌性大鼠模型,随机分成Exenatide组(EX组,10只),给予EX颈部皮下注射;二甲双胍组(MF组,10只),给予MF无菌蒸馏水溶解灌胃;PCOS组(9只)及正常对照组(NC组,10只)。连续给药4周后检测各组大鼠血清空腹胰岛素(FINS)、并进行糖耐量试验(OGTT),计算HOMAIR指数。采用免疫组化及Real-time PCR法测定各组大鼠胰腺SIRT1的表达情况。【结果】1免疫组化和Q-PCR在蛋白水平和m RNA水平表明SIRT1表达于正常的胰腺内分泌组织中。PCOS组与NC组相比SIRT1表达明显降低(P<0.05),经过药物干预后的EX和MF组与PCOS组相比表达均有不同程度升高(P<0.05),而EX和MF之间相比没有统计学差异。2SIRT1表达与血清FPG、FINS、HOMA-IR呈明显负相关。【结论】Exenatide的干预改善了大鼠的血糖水平和胰岛素抵抗状态。SIRT1的表达下降可能在PCOS的发生发展中具有重要作用,Exenatide可能会通过上调SITR1的表达具有治疗PCOS的潜在作用。

【Objective】 To observe the effect of Exenatide on the expression of SIRT1 in pancreas tissue of rat with polycystic ovary syndrome,and discuss the intervention effect of Exenatide for PCOS rats and its possible mechanisms.【Methods】 Establishment of PCOS animal model（n = 50）,the others were randomly devided into Exenatide treatment group（EX group,n = 10）,administered Exenatide hypodermic injection.Metformin treatment group（MF group,n = 10）,given metformin per os dissolved in distilled water.Control group（PCOS group,n = 9） and natural group（natural group,n = 10）.The treatment period was four weeks and detected the FINS of rats serum,and experimented oral glucose tolerance test（OGTT） and used HOMA-IR to assess insulin resistance.To detect the expression of SIRT1 in the pancreas tissue of every group rats through real-time PCR and immunohistochemistry.【Results】 1.RTPCR and immunohistochemistry showed that SIRT1 expressed in normal pancreatic endocrine tissue.The level of SIRT1 m RNA in PCOS group was significantly lower than that in the natural group（P〈0.05）,after drug intervention MF,EX group were to varying degrees higher than PCOS group（P〈0.05）.There was no statistical difference between MF group and EX group.2.There is a significantly negative correlation between the expression SIRT1 and FPG,2h PG,FINS,and HOMA-IR levels.【Conclusions】Exenatide intervention weliorate the state of blood glucose and insulin resistance in rats with PCOS.Decreased expression of SIRT1 may play an important role in the development of PCOS,and Exenatide could upregulate the SIRT1 expression and provide a potential method for PCOS treatment.