艾塞那肽对多囊卵巢综合征大鼠胰岛素抵抗及生殖激素的影响

Effect of Exenatide on Insulin Resistance and Reproductive Hormone in Polycystic Ovary Syndrome Rats

【目的】探讨艾塞那肽(Exenatide)在多囊卵巢综合征(PCOS)大鼠胰岛素抵抗及生殖内分泌方面的作用。【方法】采用脱氢表雄酮(DHEA)诱导建立PCOS雌性大鼠模型。建模成功后将大鼠随机分成4组:Exenatide组(EX组,10只),二甲双胍组(MF组,10只),多囊卵巢综合征组(PCOS组,9只)及正常对照组(NC组,10只)。EX组给予Exenatide颈部皮下注射;MF组给予二甲双胍用无菌蒸馏水溶解灌胃;PCOS组和对照组每天给予正常饮食。连续给药4周后在光学显微镜下HE染色观察各组大鼠卵巢组织学改变;检测各组大鼠血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH),糖耐量试验(OGTT)、空腹胰岛素(FINS)并计算HOMA-IR指数。【结果】PCOS大鼠模型建立成功。药物干预后血清激素T、LH:EX、MF、NC组显著低于PCOS组(P<0.05);LH/FSH:EX组低于PCOS组(P<0.05)。药物干预后血清FPG、FINS、HOMA-IR:EX、MF、NC组低于PCOS组(P<0.05),30 min PG:EX、PCOS、NC组低于MF组(P<0.05)。1h PG:EX、NC组低于MF、PCOS组(P<0.05)。2h PG:MF、EX、NC组低于PCOS组(P<0.05)。【结论】Exenatide的干预改善了PCOS大鼠的胰岛素抵抗,降低HOMA-IR、LH/FSH比值及雄激素水平,改善内分泌紊乱,进而改善卵巢功能,为PCOS治疗提供新的途径。

[ Objective ] To study the effect of exenatide on PCOS IR and reproductive endocrine hormone in PCOS rats. [ Methods ] We used the dehydroepiandrosterone （DHEA） to establish female PCOS rats modeland the rats were randomly divided into exenatide treatment group （Group EX, n = 10）, metformin treatment group （Group MF, n = 10）, PCOS group （Group PCOS, n = 9）, and normal control group （Group NC, n = 10）. The EX group was administered exenatide hypodermic injection once daily, while MF group was given mefformin per os dissolved in distilled water once daily, the treatment period was four weeks. The Group PCOS and Group NC were given the normal diet. Histologi＇c detection of ovaries by HE staining the ovary tissue of every group rats were observed their pathohistology by lighter microscope. Detecting the T, FSH, LH, OGTF, FINS of rats serum, and using HOMA-IR to assess insulin resistance. [Results] 1. The rat model of＇PCOS was successfully established. 2. After drug intervention the values of T and LH： MF, EX, NC group were lower than PCOS group （P 〈 0.05）. LH/FSH：EX group were lower than PCOS group （P 〈 0.05）. 3. After drug intervention the values of FPG, FINS, HOMA-IR： MF, EX, NC group were lower than PCOS group （P 〈 0.05）. The values of 30minPG： MF group was higher than EX, PCOS, and NC group （P〈 0.05）. The values of lhPG： MF and PCOS group were higher than EX and NC group （P 〈 0.05）. The values of 2hPG： PCOS group was higher than EX, MF, and NC group （P 〈 0.05）. [Conclusions] Exenatide improves insulin resistance and reproductive in PCOS rats, reducing HOMA-IR, LH/FSH ratio and androgen levels, ameliorate endocrine disorders, thereby improving ovarian function and promote follicle development, providing new avenues for the treatment of PCOS.