目的 探讨红花黄色素对大鼠多囊卵巢综合征及Toll受体4/核转录因子-κB/NOD样蛋白受体3（TLR4/NF-κB/ NLRP3）信号通路的影响。方法 实验设置对照组、模型组、红花黄色素组、红花黄色素＋TLR4抑制剂（TAK242）组和红花黄色素＋TLR4激动剂脂多糖（LPS）组，每组8只大鼠。除对照组外，其他组大鼠均通过连续21 d ig来曲唑的方法制备多囊卵巢综合征动物模型。各组分别ip给药28 d后，测定大鼠空腹血糖和空腹胰岛素水平，计算胰岛素抵抗指数；ELISA法测定血清性激素和炎症因子水平；HE染色观察卵巢和子宫内膜组织病理形态，计数卵巢组织囊性扩张卵泡数、黄体数和子宫内膜组织腺体数，测量子宫内膜厚度；Western blotting检测卵巢和子宫内膜组织TLR4/NF-κB/NLRP3信号通路蛋白表达。结果 与模型组相比，红花黄色素组空腹血糖、空腹胰岛素、胰岛素抵抗指数、睾酮（T）、促黄体生成素（LH）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-18水平和LH/FSH明显降低，雌二醇（E₂）、促卵泡生成素（FSH）水平明显升高（P＜0.05）；卵巢和子宫内膜组织病理学形态结构改变明显改善，卵巢组织囊性扩张卵泡数明显降低，卵巢组织黄体数、子宫内膜组织腺体数及子宫内膜厚度均明显升高（P＜0.05）；卵巢和子宫内膜组织中TLR4、NF-κB、p-NF-κB、NLRP3蛋白表达水平及p-NF-κB/NF-κB比值明显降低（P＜0.05）。与模型组相比，红花黄色素＋TAK242组可进一步下调TLR4/NF-κB/NLRP3信号通路，明显增强红花黄色素对多囊卵巢综合征大鼠胰岛素抵抗、性激素、炎症因子、卵巢和子宫内膜组织病理改变的调控作用；而红花黄色素＋LPS组则上调TLR4/NF-κB/NLRP3信号通路，明显减弱红花黄色素上述作用（P＜0.05）。结论 红花黄色素能够抑制多囊卵巢综合征大鼠炎症反应，改善卵巢功能和子宫内膜容受性，作用机制可能与下调TLR4/NF-κB/NLRP3信号通路有关。

Objective To investigate the effect of safflower yellow on polycystic ovary syndrome in rats and the TLR4/NF-κB/NLRP3 signaling pathway. Methods The experimental setup included control group, model group, safflower yellow group, safflower yellow + TLR4 inhibitor (TAK242) group, and safflower yellow + TLR4 agonist (LPS) group, with 8 rats in each group. Except for the control group, the rats in other groups were prepared with polycystic ovary syndrome model by continuously oral gavage with letrozole for 21 d. After intraperitoneal injection for 28 d, the fasting blood glucose and fasting insulin levels were measured, and the homeasis model assessment of insulin resistance was calculated. The level of sex hormones and inflammatory factors in serum were detected by ELISA method. The tissues pathological morphology of ovarian and endometrial were observed by HE staining, the number of cystic follicles, corpus luteum in ovarian tissue and the number of glands in endometrium were counted, the endometrial thickness was measured. The expression of TLR4/NF-κB/NLRP3 signaling pathway related proteins in ovarian and endometrial tissues were detected by Western blotting. Results Compared with the model group, the level of fasting blood glucose, fasting insulin, insulin resistance index, T, LH, TNF-α, IL-1β, IL-18, and LH/FSH in safflower yellow group were significant decreased, while the level of E₂, and FSH were significant increased (P < 0.05). The pathological changes in ovarian and endometrial tissues were significantly improved, the number of cystic follicles in ovarian was significantly decreased, the number of corpus luteum in ovarian was significantly increased, the number of glands in endometrium and the endometrial thickness were significantly increased (P < 0.05). The expression level of TLR4, NF-κB, p-NF-κB, NLRP3 proteins and the ratio of p-NF-κB/NF-κB in ovarian and endometrial tissues were significantly decreased (P < 0.05). Safflower yellow + TAK242 group could further downregulate the TLR4/NF-κB/NLRP3 signaling pathway, significantly enhancing the regulatory effect of safflower yellow on insulin resistance, sex hormones, inflammatory factors, ovarian and endometrial tissue pathological changes in polycystic ovary syndrome rats, safflower yellow + LPS upregulated the TLR4/NF-κB/NLRP3 signaling pathway and thus significantly weakened the aforementioned effects of safflower yellow (P < 0.05). Conclusion Safflower yellow could suppress the inflammatory response in polycystic ovary syndrome rats, improve ovarian function and uterine receptivity, which mechanism may be related to the down-regulation of TLR4/NF-κB/NLRP3 signaling pathway.

R287.4

河北省医学科学研究课题计划（20220559）