针药干预对多囊卵巢综合征胰岛素抵抗模型大鼠生殖内分泌及PI3K/Akt信号通路的影响

Effects of Acupuncture and Medicinal Herbs on the Reproductive Endocrines and PI3K/Akt signaling pathway in polycystic ovary syndrome with insulin resistance model

目的观察针刺联合五子衍宗丸对多囊卵巢综合征胰岛素抵抗(PCOS-IR)模型大鼠生殖内分泌及PI3K/Akt信号通路的影响,探讨其可能作用机制。方法雌性Wistar大鼠随机分为空白对照组、模型组、二甲双胍组和针药联合组,每组8只,除空白对照组外其余各组项背部皮下注射脱氢表雄酮(DHEA)建立PCOS-IR模型。造模成功后各组行干预治疗(连续28天)。采用HE染色法观察卵巢组织变化;ELISA法检测卵泡刺激素(FSH)、雌二醇(E_2)、黄体生成素(LH)和睾酮(T)水平及空腹胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);实时荧光定量PCR法检测卵巢组织胰岛素受体底物1(IRS-1)和磷脂酰肌醇3激酶(PI3K)mRNA表达情况。结果与正常组比较,模型组卵巢呈多囊样改变,闭锁卵泡增多,未见黄体分布,且模型组血清FSH、E_2、LH和T水平改变,卵巢组织IRS-1和PI3K mRNA表达下降;与模型组比较,二甲双胍组和针药联合组可见不同发育阶段的卵泡及少量黄体,血清FSH、E_2水平明显升高(P<0.01),LH、T水平明显降低(P<0.01),FINS水平及HOMA-IR值明显降低(P<0.01),卵巢组织IRS-1和PI3K mRNA表达上调(P<0.01)。结论针药联合可以改善PCOS-IR模型大鼠生殖内分泌水平以及胰岛素抵抗情况,可能与PI3K/Akt信号通路的调控有关。

Objective To observe the effect of acupuncture and medicinal herbs on the reproductive endocrine and PI3K/Akt signaling pathway in polycystic ovary syndrome with insulin resistance（ PCOS-IR） model rats and to explore its mechanism. Methods Female Wistar rats were randomly divided into control group, model group, met- formin group and combination of acupuncture and medicinal herbs group. Each group consisted of eight rats. PCOS-IR model was established bv subcutaneous iniection of dehvdroepiandro-sterone（DHEA） in Wistar rats.Con-tinuous treatment for 28 days after the success of modeling.HE staining was used to observe the changes of ovarian morphology. Serum levels of follicle-stimulating hormone （ FSH ）, estradiol （ E2 ）, luteinizing hormone （ LH ）, testoster- one（T） and fasting insulin （FINS）were measured by ELISA. Fasting plasma glucose （FPG）was measured by blood glucose meter, and homeostasis model assessment-insulin resistance index （HOMA- IR ）was calculated. Realtime PCR technique was used to detect the expression of IRS-1 and PI3K mRNA in ovarian tissue.Results Compared with the control group, the ovary of the model group showed more cystic changes, the atretie follicles were increased and the diameter was larger.The corpus luteum was not seen and the level of serum FSH, LH, E2 and T levels have changed.Ovarian tissue IRS-1 and PI3K mRNA expression decreased compared with the model group,the levels of serum FSH and E2 were significantly increased（ P〈0.01 ）, LH and T were significantly decreased （ P〈0.01 ） .The levels of FINS and HOMA-IR in each group were lower than those in model group （P〈0.01）.The expression of IRS-1 and PI3K mRNA of ovarian tissue was significantly increased（ P〈0.01 ）.Conclusion The acupuncture and medicinal herbs can improve the level of reproductive endocrine and insulin resistance which may be related to the regulation of PI3K/Akt signaling pathway.