Mechanism of Cai’s Neiyi Prescription regulating TRIM24/NLRP3 inflammasome-mediated endometriotic pyroptosis in rats

Yuanyuan HANG; Li TAN; Yang CAO; Mengfei ZHUANG; Yuli JIN

doi:10.16305/j.1007-1334.2021.2011078

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Mechanism of Cai’s Neiyi Prescription regulating TRIM24/NLRP3 inflammasome-mediated endometriotic pyroptosis in rats

更新时间：2022-08-03

- Mechanism of Cai’s Neiyi Prescription regulating TRIM24/NLRP3 inflammasome-mediated endometriotic pyroptosis in rats
- Shanghai Journal of Traditional Chinese Medicine Vol. 55, Issue 9, Pages: 74-80(2021)
- 作者机构：
  
  1.上海交通大学附属第一人民医院中医科（上海　200080）
  2.上海中医药大学附属岳阳中西医结合医院妇科（上海　200437）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2021.2011078
  CLC：
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Yuanyuan HANG, Li TAN, Yang CAO, et al. Mechanism of Cai’s Neiyi Prescription regulating TRIM24/NLRP3 inflammasome-mediated endometriotic pyroptosis in rats. [J]. Shanghai Journal of Traditional Chinese Medicine 55(9):74-80(2021)
DOI：

Yuanyuan HANG, Li TAN, Yang CAO, et al. Mechanism of Cai’s Neiyi Prescription regulating TRIM24/NLRP3 inflammasome-mediated endometriotic pyroptosis in rats. [J]. Shanghai Journal of Traditional Chinese Medicine 55(9):74-80(2021) DOI： 10.16305/j.1007-1334.2021.2011078.

摘要

目的,2,探讨蔡氏内异方是否通过作用于TRIM24/NLRP3炎症小体介导的细胞焦亡而干预子宫内膜异位症。,方法,2,采用子宫内膜自体移植法建立大鼠子宫内膜异位症模型。SD雌性大鼠随机取6只为正常对照组，6只为假手术组，其余大鼠造模成功后，再随机分为模型组、孕三烯酮组（0.25 mg/kg）、蔡氏内异方低剂量组（11.4 g/kg）、蔡氏内异方高剂量组（22.8 g/kg），每组6只。灌胃3周后，将各组大鼠的子宫内膜组织进行HE染色以观察组织形态，并采用IHC染色检测TRIM24的表达，Western blot法检测TRIM24及NLRP3炎症小体介导的细胞焦亡相关蛋白的表达，ELISA法检测组织上清液中IL-1β、IL-18的浓度。,结果,2,与正常对照组比较，假手术组的子宫内膜组织形态、TRIM24的表达、NLRP3炎症小体介导的细胞焦亡相关蛋白的表达及IL-1β、IL-18的浓度均无明显差异。与假手术组比较，模型组的组织上皮层增厚且不规则， TRIM24的表达显著降低（,P,<,0.001），NLRP3炎症小体介导的细胞焦亡相关蛋白的表达明显升高，IL-1β、IL-18的浓度显著升高（,P,<,0.001）。与模型组比较，孕三烯酮组和蔡氏内异方高剂量组的组织上皮层变薄且规则，TRIM24的表达显著升高（,P,<,0.001，,P,<,0.01），NLRP3炎症小体介导的细胞焦亡相关蛋白的表达明显降低，IL-1β、IL-18的浓度显著降低（,P,<,0.001）。与孕三烯酮组比较，蔡氏内异方低剂量组的上皮细胞增多，蔡氏内异方高剂量组的间质细胞增多。与蔡氏内异方低剂量组比较，蔡氏内异方高剂量组的组织上皮层变薄，间质中TRIM24的表达明显增加，Pro-IL-1β蛋白的表达明显降低（,P,<,0.01）。,结论,2,高剂量蔡氏内异方可显著上调异位子宫内膜组织中TRIM24的表达，并明显抑制NLRP3炎症小体介导的细胞焦亡。

Abstract

Objective,2,To explore whether Cai’s Neiyi Prescription treats endometriosis by acting on pyroptosis mediated by TRIM24/NLRP3 inflammasome.,Methods,2,SD female rats, six rats were randomly selected as normal control group and six rats as sham operation group. After established the endometriotic model by endometrial autotransplantation method, model rats were randomly divided into model group, gestrinone group (0.25 mg/kg), and low-dose group (11.4 g/kg) and high-dose group(22.8 g/kg) of Cai’s Neiyi Prescription, with 6 rats in each group. After three weeks of intragastric administration, the endometrium of each group was stained with HE for observing the tissue morphology. Meanwhile, immunohistochemistry(IHC) was used to detect the expression of TRIM24, and Western blot was used to detect the protein expression of TRIM24 and NLRP3 inflammasome-mediated pyroptotic proteins, and ELISA was used to detect the concentration of IL-1β and IL-18 in the supernatant fluid of endometrial tissues. there was no significance in the morphology of endometrial tissues, TRIM24 expression, the protein expression of NLRP3 inflammasome-mediated pyroptotic proteins and the concentration of IL-1β and IL-18 in the sham operation group. Compared with the sham operation group, the epithelial layers were thickened and irregular, and TRIM24 expression was significantly decreased (,P,<,0.001), while the protein expression of NLRP3 inflammasome-mediated pyroptotic proteins was obviously increased, and the concentration of IL-1β and IL-18 was significantly elevated (,P,<,0.001) in the model group. Compared with the model group, the epithelial layers were thinned and regular, and TRIM24 expression was significantly promoted (,P,<,0.001,P,<,0.01), while the protein expression of NLRP3 inflammasome-mediated pyroptotic proteins was obviously decreased, and the concentration of IL-1β and IL-18 was obviously reduced (,P,<,0.001) in the gestrinone group and high-dose group of Cai’s Neiyi Prescription. Compared with the gestrinone group, epithelial cells were increased in the low-dose group of Cai’s Neiyi Prescription, and stromal cells were elevated in the high-dose group of Cai’s Neiyi Prescription. Compared with the low-dose group of Cai’s Neiyi Prescription, the epithelial layers were thinned, and expression of TRIM24 in the stromata was notably promoted, but the protein expression of Pro-IL-1β was reduced significantly (,P,<,0.01) in the high-dose group of Cai’s Neiyi Prescription.,Conclusion,2,Cai’s Neiyi Prescription with high dose can significantly up-regulate TRIM24, and inhibit NLRP3 inflammasome-mediated pyroptosis in ectopic endometrial tissues.

关键词

蔡氏内异方子宫内膜异位症模型大鼠TRIM24NLRP3炎症小体IL-1βIL-18中药研究

Keywords

Cai’s Neiyi Prescriptionendometriosismodel ratsTRIM24NLRP3 inflammasomeIL-1βIL-18traditional Chinese herbal medicine research

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