南方医科大学学报2024，Vol.44Issue(8)：1467-1475,9.DOI:10.12122/j.issn.1673-4254.2024.08.05
血根碱通过调控Nrf2/NF-κB通路缓解小鼠溃疡性结肠炎
Sanguinarine alleviates ulcerative colitis in mice by regulating the Nrf2/NF-κB pathway
摘要
Abstract
Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.关键词
溃疡性结肠炎/血根碱/Nrf2/NF-κBKey words
ulcerative colitis/sanguinarine/Nrf2/nuclear factor-κB引用本文复制引用
赵娜,沈梦迪,赵睿,奥迪,骆泽谭,张银亮,徐志东,范方田,郑海伦..血根碱通过调控Nrf2/NF-κB通路缓解小鼠溃疡性结肠炎[J].南方医科大学学报,2024,44(8):1467-1475,9.基金项目
安徽省高等学校科学研究项目(自然科学类)重大项目(No.2022AH051489) （自然科学类）
