基于分子对接技术探讨巴戟天改善子宫内膜容受性的机制

Exploration of the mechanism of Morinda officinalis in improving endometrial receptivity based on molecular docking technology

目的运用分子对接技术分析巴戟天改善子宫内膜容受性的作用机制。方法将60只Wistar雌性大鼠随机分为正常组、模型组、枸橼酸氯米芬组、巴戟天组,每组15只。模型组、枸橼酸氯米芬组和巴戟天组构建不孕症大鼠模型;正常组、模型组给予生理盐水2 mL灌胃,1次/d;枸橼酸氯米芬组给予0.83 mg/mL枸橼酸氯米芬溶液2 mL灌胃,1次/d;巴戟天组给予0.5 g/mL巴戟天溶液2 mL灌胃,2次/d。给药15 d后取大鼠子宫检测,比较子宫内膜厚度、子宫内膜下血流参数[子宫动脉搏动指数(PI)、阻力指数(RI)、收缩期/舒张期流速比值(S/D)]和内皮型一氧化氮合酶(eNOS)、血管内皮生长因子(VEGF)蛋白表达水平。结合实验结果,通过网络药理学分析巴戟天可能的作用机制,并通过分子对接预测活性成分的结合部位。结果与正常组比较,模型组大鼠子宫内膜厚度、PI、RI、eNOS、VEGF降低,S/D升高(P<0.05)。与模型组比较,枸橼酸氯米芬组大鼠子宫内膜厚度、PI、RI、eNOS、VEGF升高,枸橼酸氯米芬组大鼠S/D降低(P<0.05)。与枸橼酸氯米芬组比较,巴戟天组大鼠子宫内膜厚度、PI、RI、eNOS、VEGF升高,巴戟天组大鼠S/D降低(P<0.05)。网络药理学共筛选出巴戟天有效成分199种,子宫内膜容受性相关靶点792个,其交集靶点99个。PPI网络分析巴戟天主要作用于ESR1、NCOA1、NCOA2、MAPK14、PGR和AR等关键靶点。分子对接结果表明筛选得到的主要活性成分与靶点有较强的结合。结论巴戟天对改善子宫内膜容受性或许具有积极作用,其作用机制可能与调节ESR1、NCOA1、NCOA2、MAPK14、PGR和AR等信号通路有关。

Objective To analyze the mechanism of Morinda officinalis in improving endometrial receptivity by molecular docking technique.Methods A total of 60 Wistar female rats were randomly divided into normal group,model group,clomiphene citrate group and morinda group,with 15 rats in each group.Infertility rat models were constructed in model group,clomiphene citrate group and morinda group.Normal group and model group were given 2 mL normal saline intragastric administration,once a day.Clomiphene citrate group was given 0.83 mg/mL clomiphene citrate solution 2 mL intragastric administration,once a day.Morinda group was given 0.5 g/mL Morinda officinalis solution 2 mL intragastric administration,twice a day.The endometrial thickness,subendometrial blood flow parameters[uterine arterial pulse index(PI),resistance index(RI),systolic/diastolic flow rate ratio(S/D)],and the protein expression levels of endothelial nitric oxide synthase(eNOS)and vascular endothelial growth factor(VEGF)were compared 15 days after administration.Combined with the experimental results,the possible mechanism of action of Morinda officinalis was analyzed by network pharmacology,and the binding sites of active ingredients were predicted by molecular docking.Results Compared with normal group,endometrial thickness,PI,RI,eNOS and VEGF were decreased and S/D was increased in model group(P<0.05).Compared with model group,endometrial thickness,PI,RI,eNOS and VEGF were increased in clomiphene citrate group,while S/D was decreased in clomiphene citrate group(P<0.05).Compared with clomiphene citrate group,endometrial thickness,PI,RI,eNOS and VEGF were increased in morinda group,while S/D was decreased in morinda group(P<0.05).A total of 199 active ingredients of Morinda officinalis were identified by network pharmacology,including 792 endometrial receptivity related targets and 99 intersection targets.Protein-protein interaction(PPI)network analysis of Morinda officinalis mainly acts on ESR1,NCOA1,NCOA2,MAPK14,PGR,AR and other key targets.The results of molecular docking showed that the main active ingredients obtained by screening had strong binding with the target.Conclusions Morinda officinalis may have positive effects on endometrial receptivity,and its mechanism may be related to the regulation of ESR1,NCOA1,NCOA2,MAPK14,PGR and AR signaling pathways.