紫杉醇调控TLR4/NF-κB/NLRP3信号通路对多囊卵巢综合征大鼠卵巢颗粒细胞生物学行为的影响  

To investigate the effect of paclitaxel on the biological behavior of ovarian granulosa cells in rats with polycystic ovary syndrome by regulating TLR4/NF-κB/NLRP3 signaling pathway

作　　者：陈思文 胡卫华[1] 严永旭[1] 姜根风 洪程程 江海波[1] CHEN Siwen;HU Weihua;YAN Yongxu;JIANG Genfeng;HONG Chengcheng;JIANG Haibo(Department of Reproductive Medicine,Yijishan Hospital,Wannan Medical College,Wuhu 241000,China)

机构地区：[1]皖南医学院弋矶山医院生殖医学科,安徽芜湖241000

出　　处：《山东第一医科大学（山东省医学科学院）学报》2024年第12期705-709,共5页Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences

基　　金：安徽省卫生健康委员会重点项目(AHWJ2022a002);皖南医学院中青年科研基金项目(WK2023ZQNZ30);芜湖市科技成果转化项目(2022cg24)。

摘　　要：目的 探究紫杉醇调控TLR4/NF-κB/NLRP3信号通路对多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠卵巢颗粒细胞生物学行为的影响。方法 构建PCOS大鼠模型并提取卵巢颗粒细胞进行培养鉴定,将卵巢颗粒细胞随机分为PCOS组、PCOS+紫杉醇低剂量组、PCOS+紫杉醇中剂量组、PCOS+紫杉醇高剂量组、PCOS+紫杉醇+Toll样受体4(Toll-like receptors 4,TLR4)制剂组。ELISA实验检测雌二醇(estradiol,E2)、雄激素(testosterone,T)、孕酮(progesterone,P)、黄体生成素(luteinizing hormone,LH)、促卵泡生成素(follicle-stimulating hormone,FSH)含量;CCK8实验检测各组细胞增殖能力,Transwell实验检测细胞迁移能力,流式细胞术测定各组细胞凋亡率,蛋白免疫印迹实验检测TLR4、核因子-κB(nuclear factor kappa-B,NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、caspase-3蛋白水平。结果 紫杉醇各剂量治疗组和TLR4抑制剂组对正常颗粒细胞增殖能力没有影响,但能够显著提升PCOS组细胞的增殖能力。与PCOS组相比,紫杉醇各剂量治疗组和TLR4抑制剂组细胞中的E2、T、LH含量明显减少,细胞的迁移能力显著增强、凋亡数明显减少;细胞内的TLR4、NF-κB、NLRP3、caspase-3蛋白表达水平均明显下调,差异均有统计学意义(P均<0.05)。结论 紫杉醇能促进PCOS大鼠卵巢颗粒细胞的增殖、迁移,抑制其凋亡,其调控机制可能与调控TLR4/NF-κB/NLRP3信号通路有关。Objective:To investigate the effect of paclitaxel on the biological behavior of ovarian granulosa cells in rats with polycystic ovary syndrome(PCOS)by regulating TLR4/NF-κB/NLRP3 signaling pathway.Methods:A rat model of polycystic ovary syndrome was established and ovarian granulosa cells were isolated for culture and identification.Ovarian granulosa cells were randomly divided into PCOS group,PCOS+paclitaxel low dose group,PCOS+paclitaxel middle dose group,PCOS+paclitaxel high dose group,PCOS+paclitaxel+TLR4 inhibitor group,and normal granulosa cells were used as control group.Estradiol(E2),testosterone(T),progesterone(P),luteinizing hormone(LH)and follicle-stimulating hormone(FSH)were detected by ELISA.CCK8 assay was used to detect the cell proliferation ability of each group.Transwell assay was used to detect the cell migration ability,.Flow cytometry was used to detect the cell apoptosis rate of each group,and Western blot was used to detect the protein levels of TLR4,NF-κB,NLRP3 and caspase-3.Results:All doses of paclitaxel and TLR4 inhibitor had no effect on the proliferation of normal granulosa cells,but significantly increased the proliferation of PCOS cells.Compared with the PCOS group,the levels of E2,T and LH in the paclitaxel treatment groups and TLR4 inhibitor group significantly decreased,the cell migration ability enhanced significantly,and the number of apoptosis significantly reduced.The protein expression levels of TLR4,NF-κB,NLRP3 and Caspase3 in the cells were significantly down-regulated(P<0.05).Conclusion:Paclitaxel can promote the proliferation,migration and inhibit the apoptosis of ovarian granulosa cells in rats with PCOS,and its regulatory mechanism may be related to the regulation of TLR4/NF-κB/NLRP3 signaling pathway.

关 键 词：紫杉醇 TLR4/NF-κB/NLRP3 多囊卵巢综合征 

分 类 号：R965[医药卫生—药理学]