目的 研究抑瘤汤对上皮性卵巢癌中NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体的作用。方法 通过免疫组化法比较人体的良性肿物和卵巢癌组织中NLRP3和白细胞介素（IL）-1β的表达水平；体外培养人上皮性卵巢癌细胞系A2780，分成对照组、化疗（给予DMSO溶解的紫杉醇100nmol·L^-1）组、化疗＋抑瘤汤（1、10、100mg·L^-1）组，对照组加入等量DMSO，干预12、24、48、72h后，CCK-8法检测细胞存活率，选取合适的抑瘤汤浓度及干预时间进行后续实验；Western blotting法检测NLRP3的蛋白表达；实时荧光定量PCR（qRT-PCR）法检测NLRP3、半胱氨酸蛋白酶-1（Caspase-1）、凋亡相关斑点样蛋白（ASC）和IL-1β的mRNA水平；ELISA法检测细胞上清液中NLRP3、Caspase-1、ASC和IL-1β蛋白水平。结果 与卵巢良性肿物组相比，卵巢癌患者的卵巢组织中NLRP3及IL-1β蛋白表达显著上调（P＜0.05）；干预24、48、72h后，与对照组相比，化疗组的细胞存活率显著降低（P＜0.05、0.001）；与化疗组相比，化疗＋100mg·L^-1抑瘤汤组的细胞存活率显著降低（P＜0.01、0.001），选取100mg·L^-1抑瘤汤干预48h进行后续研究。与对照组相比，化疗组的细胞中NLRP3蛋白表达水平降低，但无统计学意义；与对照组及化疗组相比，化疗＋抑瘤汤组的细胞中NLRP3蛋白表达水平显著降低（P＜0.05、0.001）。与对照组相比，化疗组和化疗＋抑瘤汤组的NLRP3 mRNA和上清中蛋白水平显著降低（P＜0.05、0.001）；与化疗组相比，化疗＋抑瘤汤组的NLRP3mRNA和上清中蛋白水平显著降低（P＜0.05）。与对照组相比，化疗组的Caspase-1、ASC、IL-1β的mRNA水平降低，但无统计学意义；化疗＋抑瘤汤组的Caspase-1、ASC、IL-1β mRNA水平显著降低（P＜0.05）。与对照组相比，化疗组和化疗＋抑瘤汤组细胞上清中的Caspase-1、ASC、IL-1β蛋白水平显著降低（P＜0.01、0.001）；与化疗组相比，化疗＋抑瘤汤组的Caspase-1、ASC、IL-1β蛋白进一步降低，其中Caspase-1、ASC差异显著（P＜0.05、0.001）。结论 NLRP3炎症小体在卵巢癌中高表达，抑瘤汤可抑制卵巢癌细胞NLRP3炎症小体的表达。

Objective To study the effect of Yiliu Decoction on Nod-like receptor pyrin domain 3 (NLRP3) inflammasome in epithelial ovarian cancer.Methods Expression of NLRP3 and interleukin (IL) -1β in benign tumor and ovarian cancer patients were compared by immunohistochemistry. Human epithelial ovarian cancer cell line A2780 was cultured in vitro and divided into control group, chemotherapy (DMSO-dissolved paclitaxel 100 nmol·L^-1) group, chemotherapy + Yiliu Decoction (1, 10 and 100 mg·L^-1) group. The control group was treated with DMSO. After 12, 24, 48 and 72 h, survival rate of cells was detected by CCK-8 method, and the appropriate concentration and intervention time of antitumor soup were selected for follow-up experiments. The protein expression of NLRP3 was detected by Western blotting. The mRNA levels of NLRP3, Caspase-1, apoptosis-related spot-like protein (ASC) and IL-1β were detected by real-time quantitative fluorescence PCR (qRT-PCR). The levels of NLRP3, Caspase-1, ASC and IL-1β in the supernatant were determined by ELISA.Results Compared with benign ovarian tumor group, NLRP3 and IL-1β protein expressions in ovarian tissue of ovarian cancer patients were significantly up-regulated (P <0.05). After 24, 48, 72 h of intervention, the survival rate of cells in chemotherapy group was significantly decreased compared with control group (P <0.05, 0.001). Compared with the chemotherapy group, the survival rate of cells in the chemotherapy +100 mg·L^-1 Yiliu Decoction group was significantly decreased (P <0.01, 0.001). The 100 mg·L^-1 Yiliu Decoction was selected to intervene for 48 h for follow-up study. Compared with the control group, the expression level of NLRP3 protein in the chemotherapy group was decreased, but there was no statistical significance. Compared with the control group and the chemotherapy group, the NLRP3 protein expression level in the chemotherapy + Yiliu Decoction group was significantly decreased (P <0.05, 0.001). Compared with control group, NLRP3 mRNA and protein levels in supernatant of chemotherapy group and chemotherapy + Yiliu Decoction group were significantly decreased (P <0.05, 0.001). Compared with chemotherapy group, NLRP3 mRNA and protein levels in supernatant of chemotherapy + Yiliu Decoction group were significantly decreased (P <0.05). Compared with control group, mRNA levels of Caspase-1, ASC and IL-1β in the chemotherapy group were decreased, but there was no statistical significance. The mRNA levels of Caspase-1, ASC and IL-1β in chemotherapy + Yiliu Decoction group were significantly decreased (P <0.05). Compared with control group, the protein levels of Caspase-1, ASC and IL-1β in cell supernatant of chemotherapy group and chemotherapy + antitumor decoction group were significantly decreased (P <0.01, 0.001). Compared with the chemotherapy group, the proteins of Caspase-1, ASC and IL-1β in the chemotherapy + antitumor decoction group were further decreased, and the differences of Caspase-1 and ASC were significant (P <0.05, 0.001).Conclusion NLRP3 inflammasome is highly expressed in ovarian cancer. Yiliu Decoction inhibits the expression of NLRP3 inflammasome in ovarian cells.

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福建省中青年教师教育科研项目(JAT190249);福建省自然科学基金面上项目(2020J011041);正大天晴医学项目研究(201511669);福建省卫生计生科研人才培养项目-医学创新课题(2018-CX-44);福建省自然科学基金青创项目(2020J05061)