右归胶囊通过JAK2/STAT3通路改善高龄体外受精-胚胎移植女性卵细胞质量

Yougui Capsule Improved Follicular Quality of Elderly Women undergoing IVF-ET through JAK2/STAT3 Pathway

目的探讨右归胶囊通过干预调节络氨酸激酶2/信号传导及转录激活因子3(JAK2/STAT3)通路中关键因子JAK2、细胞周期蛋白D1(Cyclin D1)及与通路相关的超氧化物歧化酶(superoxide dismutase,SOD)水平对高龄肾阳虚体外受精-胚胎移植(in vitrofertilization-embryo transfer,IVF-ET)患者卵细胞质量的影响。方法 64例高龄肾阳虚IVF-ET女性分为治疗组(右归胶囊+西药)和安慰剂组(安慰剂+西药),每组32例。另选非肾阳虚IVF-ET(男方因素)高龄女性32例为对照组。观察前两组肾阳虚证候积分变化和各组促性腺激素(Gn)天数及用量、绒毛促性腺激素(HCG)日血雌二醇(E2)、黄体生成素(LH)、孕酮(P)水平、获卵数、优卵率、受精率、获胚数、临床妊娠率;检测JAK2/STAT3通路中关键因子JAK2、Cyclin D1蛋白表达及与通路相关的SOD水平。结果与本组治疗前比较,治疗组HCG日证候积分降低(P<0.01),且较安慰剂组积分低更明显(P<0.01)。与安慰剂组比较,治疗组和对照组Gn天数及用量减少(P<0.01),HCG日E2水平、获卵数、获胚数、优卵率、受精率、临床妊娠率均增高(P<0.05,P<0.01),SOD水平、JAK2、CyclinD1蛋白相对表达量亦升高(P<0.05)。结论右归胶囊可能是通过JAK2/STAT3通路上调SOD、JAK2、Cyclin D1水平表达,从而改善肾阳虚症状,提高高龄肾阳虚IVF-ET患者的卵细胞质量,有助于改善IVF结局。

Objective To explore the effects of Yougui Capsule on the quality of oocytes in elderly patients with Shen-yang deficiency syndrome undergoing in vitro fertilization-embryo transfer（IVF-ET） by regulating the level of key factors （including JAK2, Cyclin D1 and SOD） in JAK2/STAT3 pathway. Methods Totally 64 IVF- ET elderly patients with Shen-yang deficiency were assigned to the treatment group （Yougui Capsule ＋ Western medicine） and the placebo group（placebos ＋ Western medicine）, 32 cases in each group. Another 32 healthy elderly women （non-Shen-yang deficiency but male factor） were enrolled as the control group. The change of Shen-yang deficiency syndrome scores was observed in the treatment and placebo group before and after treatment, the amount and days of using gonadotropin （Gn）, the estradiol （E2）, luteinizing hormone （LH） and progesterone （P） level on the day of human chorionjc gonadotropin （HCG） injection, the number of retrieved oocytes and embryo, high quality oocytes rate, the fertilization and clinical pregnancy rate were also observed and calculated. JAK2/Cyclin D1 protein expression and the level of SOD associated with the JAK2/STAT3 pathway were measured in each group. Results Compared with before treatment, the syndrome scores on the day of HCG injection were significantly lower in the treatment group （P 〈0.01 ）, and it was much lower than the placebo group （P 〈0.01 ）. Compared with the placebo group, the amount and days of using Gn were significantly reduced （P 〈0.01 ）, the level of E2 on the day of HCG, the number of retrieved oocytes and embryos, the high quality oocytes rate, the fertiliza- tion and clinical pregnancy rate were significantly higher （P 〈0.05）, JAK2/Cyclin D1 protein expression and SOD level associated with the JAK2/STAT3 pathway were all increased in the treatment group and the con- trol group. Conclusion For the elderly IVF- ET patients with Shen-yang deficiency, Yougui Capsule could improve their clinical syndrome and oocytes quality by up-regulating JAK2, Cyclin D1, SOD expression in JAK2/STAT3 pathway, thus improving the outcomes of IVF- ET.