从PI3K/Akt通路探讨针刺调控PCOS子宫内膜局部IR促进胚胎着床的机制

It is one of the difficult problems to reduce the clinical pregnancy rate and increase the abortion rate after ovulation induction in clinical treatment,Insulin resistance is strongly associated with reproductive barriers.Lots of studies and our previous clinical study demonstrated acupuncture beneficial effects on improving the insulin resistance and increasing pregnancy rates,but the underlying mechanisms of its effects remain uncertain. Regarding rats model with PCOS as the research object and using the method of the abdominal acupoint acupuncture, the study apply molecular biology techniques to observe the relations between the correlation of insulin resistance in endometrium and embryonic implantation dysfunction, and evaluate the effects of acupunctune on embryo implantation and the key gene and protein expression associated with insulin signaling pathways PI3K/Akt in the endometria with PCOS rats, and investigate the mechanisms and targets.To provide the basis for clinical application,and provide theoretical basis for acupuncture combined with ovulation medicine to increase pregnancy rates and reduce the rates of abortion.

多囊卵巢综合征（PCOS）促排后妊娠率低、流产率高是临床治疗中的难点问题。胰岛素抵抗与其生殖障碍高度相关，众多研究和课题组前期临床实验表明针刺具有改善PCOS胰岛素抵抗及提高妊娠率的作用，但其作用机理仍不清楚。本研究以PCOS大鼠模型为研究对象，采用针刺腹部穴位的方法，运用分子生物学技术，探讨子宫内膜局部胰岛素抵抗与胚胎着床障碍的相关性，观察针刺对PCOS大鼠模型胚胎着床的影响，并通过观察针刺对PCOS大鼠模型子宫内膜局部胰岛素信号转导途径P13K/AKT通路中关键基因、蛋白表达的影响，阐明针刺的作用机制和作用靶点，为针刺治疗PCOS子宫内膜胰岛素抵抗的临床应用提供实验依据，为针刺与促排药结合提高PCOS 患者妊娠率、降低流产率的治疗策略提供理论基础。

子宫内膜胰岛素抵抗是多囊卵巢综合征（PCOS）患者妊娠率低、流产率高的重要原因之一。本研究以子宫内膜胰岛素抵抗为切入点，采用分子生物技术方法观察了电针对PCOS大鼠子宫内膜PI3K/AKT途径胰岛素信号传导分子表达及胚胎着床的影响。结果发现，电针能够提高PCOS大鼠妊娠率和胚泡着床数，上调PCOS大鼠子宫内膜胰岛素信号传导PI3K/AKT途径信号分子基因和蛋白的表达，其作用可被PI3Kp85阻滞剂LY294002所阻断，电针的抗胰岛素效应可能与对PI3K/AKT信号转导途径调节有关；电针对PCOS大鼠子宫内膜胰岛素信号传导通路具有保护作用，这可能是电针治疗PCOS大鼠子宫内膜抗胰岛素抵抗,促进PCOS大鼠胚胎着床，提高妊娠率,降低流产率的作用机制之一。本研究初步阐明电针治疗多囊卵巢综合征子宫内膜局部胰岛素抵抗的作用靶点，为进一步的推广使用提供了理论支持。