补肾法通过抑制内质网应激提高子宫内膜容受性研究

Kidney-tonifying Therapy Improving Endometrial Receptivity by Inhibiting Endoplasmic Reticulum Stress

目的:研究补肾法(补肾调经方)对控制性超促排卵(COH)小鼠围着床期内质网应激的影响,探讨其提高子宫内膜容受性的作用机制。方法:实验小鼠建立COH模型并给予补肾干预,观察小鼠妊娠数和胚胎种植数,于孕4 d取子宫,Western blot和实时定量PCR分析子宫组织中雌激素受体(ERα)和内质网应激相关蛋白葡萄糖调节蛋白78(GRP78)的表达变化;组织免疫荧光观察ERα和GRP78在子宫内膜的分布。结果:模型组小鼠妊娠数、胚胎种植数显著低于正常组(P<0.05);模型组小鼠ERα和GRP78在子宫内膜基质细胞、微血管内皮细胞中表达,且ERα的表达水平显著降低(P<0.05),GRP78的表达水平显著增高(P<0.05)。与模型组相比,给予补肾调经方干预后,小鼠妊娠数、胚胎种植数明显增高(P<0.05);ERα的mRNA和蛋白水平明显增高(P<0.05),GRP78的mRNA和蛋白水平显著降低(P<0.05)。结论:补肾法(补肾调经方)改善COH小鼠子宫内膜容受性,与促进ERα表达抑制子宫内膜内质网应激有关。

Objective:To study the effect of Bushen Tiaojing Recipe(kidney-tonifying and menstruation-regulating recipe)on endoplasmic reticulum stress in controlled ovarian hyperstimulation(COH)mice during peri-implantation period,and to explore its mechanism of improving endometrial receptivity.Methods:The mouse model of COH was established and kidney-tonifying intervention was given to observe the number of pregnancies and embryo implantation.The uterus was taken on the fourth day of pregnancy.The expression of estrogen receptor(ERα)and endoplasmic reticulum stress-related protein glucose regulated protein 78(GRP78)in uterine tissue was analyzed by Western blot and real-time quantitative PCR;the distribution of ERαand GRP78 in endometrium was observed by tissue immunofluorescence.Results:The numbers of pregnancies and embryo implantation in the model group were significantly lower than those in the normal group(P<0.05);the ERαand GRP78 in the model group were expressed in endometrial stromal cells and microvascular endothelial cells,the ERαsignificantly decreased(P<0.05),and the GRP78 significantly increased(P<0.05).Compared with the model group,after the intervention of Bushen Tiaojing Recipe,the number of pregnancies and embryo implantation were significantly increased(P<0.05),the mRNA and protein levels of ERαwere significantly increased(P<0.05),and the mRNA and protein levels of GRP78 were significantly decreased(P<0.05).Conclusion:Bushen Tiaojing Recipe can improve endometrial receptivity of COH mice,which is related to promoting ERαexpression and inhibiting endoplasmic reticulum stress.