基于PI3K/Akt信号通路探讨温肾助阳调周法对肾阳虚证PCOS患者性激素、胰岛素及排卵的影响

目的:探讨肾阳虚证多囊卵巢综合征(PCOS)患者子宫内膜组织中胰岛素的磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)信号通路中Akt的表达及其活化程度,并分析温肾助阳调周法对PCOS患者性激素、胰岛素及排卵的影响。方法:选取贵州中医药大学第一附属医院2017年2月至2018年7月收治的60例肾阳虚证PCOS患者,按随机数字表法分为两组,各30例。对照组采取口服炔雌醇环丙孕酮片治疗,观察组在对照组的基础上给予温肾助阳调周法治疗,两组均治疗3个月后随访。测定所有患者的性激素水平、空腹血糖及胰岛素水平,采用稳态模型评估法计算的胰岛素抵抗指数(HOMA-IR),运用蛋白免疫印迹法检测子宫内膜组织中Akt,p-Akt蛋白的表达水平。观察两组治疗前后性激素、胰岛素及排卵的情况。结果:与本组治疗前比较,治疗后两组卵泡刺激素(FSH)和黄体生成素(LH)水平均下降,雌二醇(E2)性激素水平上升(P<0.05),观察组治疗后FSH,LH水平均低于对照组,E2性激素水平高于对照组(P<0.05);与本组治疗前比较,治疗后两组FPG,FINS均明显降低(P<0.05),观察组治疗后FPG,FINS水平明显低于对照组(P<0.05);与本组治疗前比较,治疗后两组患者的HOMA-IR及血清脂联素均有明显下降(P<0.05),观察组治疗后HOMA-IR及血清脂联素明显低于对照组(P<0.05);与本组治疗前比较,治疗后两组卵巢体积、窦卵细胞数目均明显降低,子宫内膜厚度增加(P<0.05),观察组治疗后卵巢体积、窦卵细胞数目明显低于对照组,子宫内膜厚度明显大于对照组(P<0.05);与本组治疗前比较,治疗后观察组与对照组子宫内膜Akt和p-Akt蛋白明显降低,观察组治疗后子宫内膜Akt和p-Akt明显低于对照组(P<0.05)。结论:采用温肾助阳调周法可有效的改善肾阳虚证PCOS患者性激素水平,调控胰岛素,促进卵巢功能恢复,这可能与阻断Akt磷酸化,抑制PI3K/Akt信号通路活化有关。

Effect of Wenshen Zhuyang Tiaozhou Method on Sex Hormones, Insulin and Ovulation in PCOS Patients with Kidney-Yang Deficiency Syndrome Based on PI3K/Akt Signaling Pathway

Objective: To investigate the effect of Wenshen Zhuyang Tiaozhou method on sex hormones, insulin and ovulation in polycystic ovary syndrome (PCOS) patients with kidney-Yang deficiency syndrome based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Method: Totally 60 PCOS patients with kidney-Yang deficiency syndrome treated at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from February 2017 to July 2018 were selected and divided into observation group and control group according to the random number table method, with 30 cases in each group. The control group was orally treated with ethinylestradiol and cycloproterone acetate tablets, in addition to this therapy, the observation group also received Wenshen Zhuyang Tiaozhou method. Both groups were followed up after three months of treatment. Sex hormone levels, fasting plasma glucose (FPG) and fasting insulin (FINS) levels were measured in all patients. Homeostasis model assessment-insulin resistance(HOMA-IR) was calculated by homeostasis model assessment method, and the expression levels of Akt and p-Akt proteins in endometrium were detected by Western blot. Result: After treatment, the levels of FSH and LH in both groups decreased, and the level of E₂ sex hormone increased (P<0.05). After treatment, the levels of FSH and LH in observation group were lower than those in control group, whereas the level of E₂ sex hormone was higher than that in control group (P<0.05). After treatment, the levels of FPG and FINS in two groups were significantly lower (P<0.05), while the levels of FPG and FINS in observation group were significantly lower than those in control group (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in two groups decreased significantly, while the endometrial thickness increased (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in observation group were significantly lower than those in control group, and the endometrial thickness was significantly lower than that in observation group (P<0.05). After treatment, the ovarian volume and the number of sinusoidal oocytes in observation group were significantly lower than those in control group, and the endometrial thickness was larger than that of control group (P<0.05). After treatment, the Akt and p-Akt proteins in the endometrium of observation group and control group were significantly decreased, while the Akt and p-Akt proteins in the endometrium of observation group were significantly lower than those of control group (P<0.05). Conclusion: Wenshen Zhuyang Tiaozhou method can effectively ameliorate the sex hormone level, regulate insulin and promote the recovery of ovarian function in PCOS patients with kidney-Yang deficiency syndrome. This may be related to the blocking of the phosphorylation of Akt and the inhibition of the activation of PI3K/Akt signaling pathway.