苍附导痰汤通过抑制TLR4/NF-κB通路改善肥胖多囊卵巢综合征大鼠的子宫内膜容受性

ffImprovement effect of Cangfu Daotan Decoction on endometrial receptivity in obese polycystic ovary syndrome rats by inhibiting the toll-like receptor 4/nuclear factorκB pathway

目的 探讨苍附导痰汤对肥胖型多囊卵巢综合征(PCOS)大鼠子宫内膜容受性的改良作用及可能效应机制。方法 采取来曲唑溶液灌胃同时给予高脂饮食方法构建肥胖PCOS模型大鼠,将建模成功的大鼠随机分成模型组、苍附导痰组、二甲双胍组,对照组选取正常大鼠。苍附导痰组和二甲双胍组分别给予苍附导痰汤和二甲双胍片灌胃,模型组和对照组给予灭菌纯水灌胃,持续28 d。检测各组体质量、卵巢质量、子宫质量及其形态学变化,血清激素、炎症因子、血脂水平的改变;qPCR和免疫印迹法测定Toll样受体 4/ 核转录因子κB(TLR4/NF-κB)P65通路和子宫内膜容受性相关分子标记物的基因和蛋白表达。结果 与对照组比较,模型组体质量、卵巢质量增高,子宫质量下降(P<0.05或P<0.01);卵巢组织以囊性扩张卵泡为主;血清性激素、炎症因子与脂质代谢异常;子宫内膜厚度下降(P<0.01);TLR4、P65mRNA和P-P65蛋白表达上调,αvβ3、HOXA10 蛋白和mRNA表达下调(P<0.05或P<0.01)。相较于模型组,苍附导痰和二甲双胍组体质量、卵巢质量均降低,子宫质量增加(P<0.05);血清性激素、炎症因子与脂质代谢紊乱得到改善;子宫内膜增厚;TLR4、P65mRNA和P65磷酸化蛋白表达下调,αvβ3、HOXA10 蛋白和mRNA表达上调(P<0.05或P<0.01)。与二甲双胍组比较,苍附导痰汤组子宫内膜αvβ3、HOXA10蛋白表达明显上调,TLR4、P-P65蛋白表达明显下调(P<0.05)。结论 苍附导痰汤可能通过抑制TLR4/NF-κB通路的激活改善肥胖PCOS大鼠子宫内膜容受性。

Objective To investigate the improvement effect and possible effect mechanism of Cangfu Daotan Decoction on endometrial receptivity in obese polycystic ovary syndrome(PCOS)rats.Methods The obese PCOS model was constructed by gavage of letrozole solution and administration of high fat diet.The successfully modeled rats were randomly divided into the model group,the Cangfu Daotan group and the metformin group,and normal rats were selected as the control group.The Cangfu Daotan group and the metformin group received Cangfu Daotan Decoction and metformin tablets by gavage,respectively,and the model group and the control group received sterilized pure water by gavage for 28 days.The changes of body mass,ovarian mass,uterine mass and morphology,serum hormone levels,inflammatory factor levels and blood lipid levels in each group were detected.Expression of gene and protein of toll-like receptor 4/nuclear factorκB(TLR4/NF-κB)P65 pathway and molecular markers related to endometrial receptivity was determined by qPCR and Western blot.Results Compared with the control group,the body mass and ovarian mass of the model group increased,and the uterine mass decreased(P<0.05 or P<0.01);The ovarian tissue was mainly cystic dilated follicles;The levels of serum sex hormones and inflammatory factors,and lipid metabolism were all abnormal;Endometrial thickness decreased(P<0.01);The expression of TLR4,P65mRNA,and P-P65 protein was upregulated,while the expression ofαvβ3,HOXA10 protein,and mRNA was downregulated(P<0.05 or P<0.01).Compared with the model group,the body mass and ovarian mass in the Cangfu Daotan group and the metformin group were decreased,and the uterine mass was increased(P<0.05);Serum sex hormone levels,inflammatory factor levels,and abnormal lipid metabolism were all improved;The endometrium was thickened;The expression of TLR4,P65mRNA,and P65 phosphorylated protein was downregulated,while the expression ofαvβ3,HOXA10 protein,and mRNA was upregulated(P<0.05 or P<0.01).Compared with the metformin group,the expression ofαvβ3 and HOXA10 proteins in the endometrium of the Cangfu Daotan group was significantly upregulated,while the expression of TLR4 and P-P65 proteins was significantly downregulated(P<0.05).Conclusion Cangfu Daotan Decoction may improve endometrial receptivity of obese PCOS rats by inhibiting the activation of TLR4/NF-κB pathway.