基于AKT-GLUT4通路探讨二至天癸合启宫丸方对多囊卵巢综合征患者IVF-ET的影响

Effects of Erzhi Tiangui and Qigong Compound on the AKT-GLUT4 Insulin Signal Pathway of Polycystic Ovarian Syndrome and IVF-ET Outcomes

目的探讨二至天癸合启宫丸方对多囊卵巢综合征(PCOS)不孕患者卵巢局部AKT-GLUT4胰岛素代谢通路干预作用及其对妊娠结局的影响。方法选取因输卵管因素行体外受精-胚胎移植(IVF-ET)治疗的PCOS肾虚痰湿不孕患者66例,随机分为二至天癸方合启宫丸方(中药)组和安慰剂组,各组33例。两组患者皆采用GnRHa+达英-35双降方案,中药组患者于服用达英-35同时给予二至天癸方合启宫丸方,直至人体绒膜促性腺激素(HCG)注射日。安慰剂组患者给予安慰剂颗粒。观察PCOS患者治疗前后肾虚痰湿证候积分和胰岛素抵抗指标HOMA-IR变化;促性腺激素(Gn)用量和天数;获卵数、受精率、2PN卵裂率、优质胚胎率、临床妊娠率以及取卵日卵巢颗粒细胞胰岛素代谢通路中AKT、p-AKT、GLUT4蛋白水平的表达。结果中药组治疗后证候积分、HOMA-IR显著降低(P<0.01);与安慰剂组比较,中药组获卵数、受精率、优胚率、临床妊娠率增加(P<0.05,P<0.01),p-AKT、GLUT4蛋白表达升高(P<0.05);两组Gn用量、Gn天数及AKT蛋白表达比较,差异无统计学意义(P>0.05)。结论二至天癸合启宫丸方可能通过上调卵巢颗粒细胞p-AKT和GLUT4蛋白表达,改善PCOS患者卵巢胰岛素抵抗,提升卵母细胞发育潜能,进而改善PCOS患者的IVF-ET结局。

Objective To investigate the effect of Erzhi Tiangui and Qigong Compound（ ETAQC） on AKT-GLUT4 insulin signal conducting pathway inside ovaries and its effect on pregnancy outcomes of infertile patients with polycystic ovary syndrome（ PCOS）. Methods Sixty-six PCOS patients with Shen deficiency and phlegm dampness treated byin vitro fertilization-embryo transfer（ IVF-ET） were randomly and equally assigned to two groups（ 33 patients per group） ： ETAQC group（ the Chinese medicine group） and placebo group. Patients of two groups were treated with double-drop program（ GnRH-a ＋Diane 35）. Patients of ETAQC group took Diane 35 while taking ETAQC,until HCG injection day. Patients in the placebo group were given placebo granules as a contrast. Score changes of Shen deficiency and phlegm dampness symptom before and after treatment were measured,other outcomes including HOMA-IR,high-quality oocytes rate,high-quality embryos rate,clinical pregnancy rate,and the expressions of AKT,p-AKT and GLUT4 in ovarian granulosa cells on the day of retrieval were measured. Results Compared with the placebo group,the symptom score and HOMA-IR decreased significantly after treatment in ETAQC group（P〈0. 01）. In addition,ETAQC group showed a significant increasement in the oocytes number,fertilization ratio,high-quality embryos and clinical pregnancy rate（P〈0. 05,P〈0. 01）. Compared with the placebo group,the expressions of p-AKT and GLUT4 in granulosa cells of ETAQC group were increased（P〈0. 05）. The dosage and days of Gn and expression of AKT protein showed no significant difference between the two groups. Conclusion ETAQC could up-regulate the expression of p-AKT and GLUT4 in ovarian granular cells,thereby remarkably ameliorate the insulin resistance degree in the ovary tissue,so as to improve the quality of ootid and the outcome of IVF-ET patients with PCOS.