目的 探討紅花黃色素對大鼠多囊卵巢綜合征及Toll受體4/核轉(zhuǎn)錄因子-κB/NOD樣蛋白受體3（TLR4/NF-κB/ NLRP3）信號通路的影響。方法 實(shí)驗(yàn)設(shè)置對照組、模型組、紅花黃色素組、紅花黃色素＋TLR4抑制劑（TAK242）組和紅花黃色素＋TLR4激動劑脂多糖（LPS）組，每組8只大鼠。除對照組外，其他組大鼠均通過連續(xù)21 d ig來曲唑的方法制備多囊卵巢綜合征動物模型。各組分別ip給藥28 d后，測定大鼠空腹血糖和空腹胰島素水平，計算胰島素抵抗指數(shù)；ELISA法測定血清性激素和炎癥因子水平；HE染色觀察卵巢和子宮內(nèi)膜組織病理形態(tài)，計數(shù)卵巢組織囊性擴(kuò)張卵泡數(shù)、黃體數(shù)和子宮內(nèi)膜組織腺體數(shù)，測量子宮內(nèi)膜厚度；Western blotting檢測卵巢和子宮內(nèi)膜組織TLR4/NF-κB/NLRP3信號通路蛋白表達(dá)。結(jié)果 與模型組相比，紅花黃色素組空腹血糖、空腹胰島素、胰島素抵抗指數(shù)、睪酮（T）、促黃體生成素（LH）、腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素（IL）-1β、IL-18水平和LH/FSH明顯降低，雌二醇（E₂）、促卵泡生成素（FSH）水平明顯升高（P＜0.05）；卵巢和子宮內(nèi)膜組織病理學(xué)形態(tài)結(jié)構(gòu)改變明顯改善，卵巢組織囊性擴(kuò)張卵泡數(shù)明顯降低，卵巢組織黃體數(shù)、子宮內(nèi)膜組織腺體數(shù)及子宮內(nèi)膜厚度均明顯升高（P＜0.05）；卵巢和子宮內(nèi)膜組織中TLR4、NF-κB、p-NF-κB、NLRP3蛋白表達(dá)水平及p-NF-κB/NF-κB比值明顯降低（P＜0.05）。與模型組相比，紅花黃色素＋TAK242組可進(jìn)一步下調(diào)TLR4/NF-κB/NLRP3信號通路，明顯增強(qiáng)紅花黃色素對多囊卵巢綜合征大鼠胰島素抵抗、性激素、炎癥因子、卵巢和子宮內(nèi)膜組織病理改變的調(diào)控作用；而紅花黃色素＋LPS組則上調(diào)TLR4/NF-κB/NLRP3信號通路，明顯減弱紅花黃色素上述作用（P＜0.05）。結(jié)論 紅花黃色素能夠抑制多囊卵巢綜合征大鼠炎癥反應(yīng)，改善卵巢功能和子宮內(nèi)膜容受性，作用機(jī)制可能與下調(diào)TLR4/NF-κB/NLRP3信號通路有關(guān)。

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

河北省醫(yī)學(xué)科學(xué)研究課題計劃（20220559）