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LIF/LIFR/STAT3通路在多囊卵巢综合征大鼠的子宫内膜容受性中的作用 被引量:1

Role of LIF/LIFR/STAT3 pathway in endometrial receptivity in rats with polycystic ovary syndrome
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摘要 目的探讨白血病抑制因子/白血病抑制因子受体/信号转导和转录激活因子3(LIF/LIFR/STAT3)通路在多囊卵巢综合征(polycystic ovarian syndrome,PCOS)大鼠的子宫内膜容受性中的作用。方法将40只21日龄SD雌性大鼠平均分为正常(control)组、模型(model)组、假手术(sham-operation)组及LIF组,每组10只。颈后皮下注射硫酸普拉睾酮钠用于建造PCOS大鼠模型。检测每组大鼠血清中睾酮(T)、葡萄糖和胰岛素水平;HE染色观察各组大鼠子宫形态及内膜变化;免疫组化、Western blotting及实时荧光定量PCR(qRT-PCR)测定大鼠子宫内膜中LIF及STAT3的蛋白及mRNA表达,用Mann Whitney-U检验或t检验统计分析。结果与control组相比,PCOS大鼠的整合素avb3、血清T、胰岛素及葡萄糖水平明显升高(P=0.000,P=0.000,P=0.000,P=0.001),补充外源性LIF可明显降低PCOS大鼠的整合素avb3、血清T、葡萄糖及胰岛素水平(P=0.000,P=0.002,P=0.003,P=0.007)。HE结果显示,外源性LIF可改善PCOS大鼠的宫腔及腺体形态,并可增加大鼠子宫腺体及腺腔的等效直径(P=0.000,P=0.000)和面积(P=0.000,P=0.000)、腺间质面积比(P=0.000)及子宫内膜平均厚度(P=0.006),差异具有统计学意义。免疫组化、Western blotting及qRT-PCR结果显示,与control组相比,model组中LIF及p-STAT3蛋白及mRNA表达明显降低;与model组比较,LIF组中LIF及p-STAT3蛋白及mRNA表达明显升高,差异具有统计学意义(P<0.05)。结论外源性补充LIF可改善PCOS大鼠的子宫内膜容受性,其作用机制与LIF/LIFR/STAT3通路有关。 Objective To investigate the role of LIF/LIFR/STAT3 pathway in endometrial receptivity in rats with polycystic ovary syndrome(PCOS).Methods Forty 21-day-old SD female rats were divided into normal(control)group,model group,sham-operation group,and LIF group with 10 rats in each.The rat model of PCOS was constructed by subcutaneous injection of prasterone sodium sulfate at the back of the neck.The serum levels of testosterone(T),glucose and insulin in each group were detected.The morphological changes of the uterus in each group were observed by HE staining,and the morphological changes of endometrium were measured.Immunohistochemistry,Western blotting,and Real-time fluorescence quantitative PCR(qRT-PCR)were used to determine the protein expression and mRNA expression of LIF and STAT3 in rat endometrium.Results Compared with control group,the levels of integrin avb3,serum T,insulin and glucose in PCOS rats were significantly increased(P=0.000,P=0.000,P=0.001).Supplementation of exogenous LIF could significantly reduce the levels of integrin avb3,serum T,glucose and insulin in PCOS rats(P=0.000,P=0.002,P=0.003,P=0.007).HE results showed that exogenous LIF could reduce uterine cavity and glandular morphology in PCOS rats and increase the equivalent diameter(P=0.000,P=0.000)and area(P=0.000,P=0.000)of uterine glands and glandular cavity,the ratio of glandular interstitial area(P=0.000),and the average endometrial thickness(P=0.006),with statistically significant differences.Immunohistochemistry,Western blotting,and qRT-PCR results showed that the expression levels of LIF and p-STAT3 protein and mRNA in model group were significantly decreased compared with control group.Compared with model group,the protein and mRNA expressions of LIF and p-STAT3 in LIF group were significantly increased(P<0.05).Conclusion Exogenous LIF supplementation can improve endometrial receptivity in PCOS rats,and its mechanism is related to the LIF/LIFR/STAT3 pathway.
作者 袁媛 谭丽梅 张丽蓉 刘嘉文 张丽萍 YUAN Yuan;TAN Limei;ZHANG Lirong;LIU Jiawen;ZHANG Liping(Department of Gynecology,Wuhan Children’s Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,China)
出处 《西安交通大学学报(医学版)》 CAS CSCD 北大核心 2023年第6期886-892,共7页 Journal of Xi’an Jiaotong University(Medical Sciences)
基金 广西壮族自治区卫生健康委员会自筹经费科研课题-青年基金(No.Z20201345)。
关键词 多囊卵巢综合征(PCOS) 子宫内膜容受性 白血病抑制因子(LIF) 信号转导及转录激活蛋白3(STAT3) polycystic ovary syndrome(PCOS) uterine receptivity leukemia inhibitory factor(LIF) signal transducer and activator of transcription 3(STAT3)
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