梓醇联合罗格列酮调节HMGB1/TLR4/NF-κB信号通路对多囊卵巢综合征大鼠胰岛素抵抗及炎症的改善作用-东南大学学报医学版

梓醇联合罗格列酮调节HMGB1/TLR4/NF-κB信号通路对多囊卵巢综合征大鼠胰岛素抵抗及炎症的改善作用

单位：深圳市宝安区中医院妇科, 广东深圳 518000

分类号：R-33;R711.75

出版年·卷·期（页码）：2025·44·第一期（38-45）

摘要：

目的:探讨梓醇联合罗格列酮调节高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路对多囊卵巢综合征(PCOS)大鼠胰岛素抵抗及炎症的影响。方法:将72只大鼠随机分为PCOS组、梓醇组、罗格列酮组、梓醇+罗格列酮组、梓醇+罗格列酮+HMGB1激活剂(rr HMGB1)组、正常组。检测大鼠黄体生成素(LH)/促卵泡激素(FSH)、睾酮、雌二醇、空腹胰岛素、空腹血糖水平、胰岛素抵抗指数(HOMA-IR)及卵巢指数;HE染色检测卵巢组织病理;ELISA检测卵巢组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β水平;Western blotting检测TLR4、HMGB1、p-NF-κB p65/NF-κB p65蛋白。结果:与PCOS组相比,梓醇组、罗格列酮组、梓醇+罗格列酮组卵巢滤泡囊肿减少,血清中LH/FSH、睾酮水平、空腹胰岛素、空腹血糖、HOMA-IR、卵巢指数、卵巢组织中TNF-α、IL-1β水平及TLR4、HMGB1、p-NF-κB p65/NF-κB p65蛋白降低,血清中雌二醇水平升高,且梓醇+罗格列酮组对应指标变化趋势最明显(P＜0.05);rr HMGB1逆转了梓醇联合罗格列酮处理对PCOS大鼠的改善作用。结论:梓醇联合罗格列酮对PCOS大鼠胰岛素抵抗及炎症的改善作用可能与抑制HMGB1/TLR4/NF-κB通路的激活有关。

Objective: To investigate the effects of catalpol combined with rosiglitazone on insulin resistance and inflammation in rats with polycystic ovary syndrome(PCOS) by regulating high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB) pathway. Methods:72 rats were randomly divided into PCOS group, catalpol group, rosiglitazone group, catalpol+rosiglitazone group, catalpol+rosiglitazone+HMGB1 activator(rr HMGB1) group and normal group. Luteinizing hormone(LH)/follicle stimulating hormone(FSH), testosterone, estradiol, fasting insulin, fasting blood glucose levels, insulin resistance index(HOMA-IR), and ovarian index were measured in the rats. Pathological changes in ovarian tissue were detected using HE staining. Using ELISA, levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) were detected in ovarian tissue. TLR4, HMGB1, and p-NF-κB p65/NF-κB p65 proteins were detected using Western blotting. Results:Compared with the PCOS group, the ovarian follicular cysts were reduced, the levels of LH/FSH, testosterone in serum, fasting insulin, fasting blood glucose, HOMA-IR, ovarian index, levels of TNF-α, IL-1β in ovarian tissue, and TLR4, HMGB1, p-NF-κB p65/NF-κB p65 proteins were decreased, the level of estradiol in serum was increased in the catalpol group, rosiglitazone group, and catalpol+rosiglitazone group, the changes of corresponding indicators in catalpol+rosiglitazone group was the most significant(P<0.05). Rr HMGB1 reversed the improvement effect of the combination of catalpol and rosiglitazone on PCOS rats. Conclusion:The effect of catalpol combined with rosiglitazone on insulin resistance and inflammation in PCOS rats may be related to inhibiting the activation of HMGB1/TLR4/NF-κB pathway.

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