Peng Shuai, Shen Lei, Tian Min-Xiu, Li Hui-Min, Wang Shan-Shan
Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, Hubei 430060, P.R. China.
Exp Ther Med. 2021 Feb;21(2):134. doi: 10.3892/etm.2020.9566. Epub 2020 Dec 10.
Poly(ADP-ribose) polymerase-1 (PARP-1) plays a critical role in inflammatory pathways. The PARP-1 inhibitor, 5-aminoisoquinolinone (5-AIQ), has been demonstrated to exert significant pharmacological effects. The present study aimed to further examine the potential mechanisms of 5-AIQ in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Colitis conditions were assessed by changes in weight, disease activity index, colon length, histopathology and pro-inflammatory mediators. The colonic expression of PARP/NF-κB and STAT3 pathway components was measured by western blot analysis. Flow cytometry was used to analyze the proportion of T helper 17 cells (Th17) and regulatory T cells (Tregs) in the spleen. Western blot analysis and reverse transcription-quantitative PCR were employed to determine the expression of the transcription factors retinoic acid-related orphan receptor and forkhead box protein P3. The results demonstrated that 5-AIQ reduced tissue damage and the inflammatory response in mice with experimental colitis. Moreover, 5-AIQ increased the proportion of Treg cells and decreased the percentage of Th17 cells in the spleen. Furthermore, following 5-AIQ treatment, the main components of the PARP/NF-κB and STAT3 pathways were downregulated. Collectively, these results demonstrate that the PARP-1 inhibitor, 5-AIQ, may suppress intestinal inflammation and protect the colonic mucosa by modulating Treg/Th17 immune balance and inhibiting PARP-1/NF-κB and STAT3 signaling pathways in mice with experimental colitis.
聚(ADP - 核糖)聚合酶 -1(PARP -1)在炎症信号通路中发挥关键作用。PARP -1抑制剂5 - 氨基异喹啉酮(5 - AIQ)已被证明具有显著的药理作用。本研究旨在进一步探讨5 - AIQ在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型中的潜在作用机制。通过体重变化、疾病活动指数、结肠长度、组织病理学和促炎介质来评估结肠炎状况。采用蛋白质免疫印迹分析检测结肠中PARP/NF -κB和STAT3信号通路相关蛋白的表达。利用流式细胞术分析脾脏中辅助性T细胞17(Th17)和调节性T细胞(Tregs)的比例。通过蛋白质免疫印迹分析和逆转录定量PCR测定转录因子视黄酸相关孤儿受体和叉头框蛋白P3的表达。结果表明,5 - AIQ可减轻实验性结肠炎小鼠的组织损伤和炎症反应。此外,5 - AIQ可增加脾脏中Treg细胞的比例,降低Th17细胞的百分比。此外,5 - AIQ处理后,PARP/NF -κB和STAT3信号通路的主要成分表达下调。综上所述,这些结果表明,PARP -1抑制剂5 - AIQ可能通过调节Treg/Th17免疫平衡以及抑制实验性结肠炎小鼠的PARP -1/NF -κB和STAT3信号通路来抑制肠道炎症并保护结肠黏膜。