Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and fibrosis
Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and fibrosis
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穿心莲内酯磺酸盐通过减少炎症和纤维化改善 TNBS 诱导的小鼠慢性结肠炎
DOI：
10.1016/j.intimp.2020.106426
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
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作者：
Gao, Jianhua;Cui, Jian;Xu, Qiang
炎症性肠病可能导致腹泻和腹痛，以及潜在的并发症，如组织纤维化。经证实穿心莲内酯磺酸盐对2,4,6 -三硝基苯磺酸（TNBS）致小鼠急性实验性结肠炎有治疗作用。本研究建立了反复直肠内给药TNBS引发的慢性结肠炎，并考察了穿心莲内酯磺酸盐的作用。反复给药TNBS可导致大量小鼠死亡，穿心莲内酯磺酸处理可显著降低小鼠死亡。注射穿心莲内酯后，结肠组织中炎症因子IL-6、IL-17A、tnf - α和ifn - γ水平升高均降低。CD4(+) T细胞和巨噬细胞浸润下降。致病性CD4(+) T细胞亚群包括CD4(+) ifn - γ (+) （Th1）和CD4(+)IL-17A(+) （Th17）也被穿心花内酯磺酸盐抑制。此外，还观察到穿心莲内酯对p38和p65活化的抑制作用。最后，穿心莲内酯磺酸盐可显著减轻tnbs诱导的结肠上皮损伤和纤维化。基于以上结果，我们可以得出结论：穿心莲内酯磺酸盐可以减轻小鼠慢性结肠炎的炎症和上皮损伤以及纤维化，从而改善小鼠的慢性结肠炎。本研究提示临床应用穿心莲内酯磺酸盐治疗慢性结肠炎的可能性。
Inflammatory bowel disease could result in diarrhea and abdominal pain, as well as potential complications such as tissue fibrosis. The therapeutic effect of andrographolide sulfonate on acute murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) has been confirmed. In the study here, chronic colitis triggered by repeated intrarectal administration of TNBS was established and the effect of andrographolide sulfonate was examined. Repeated TNBS administration induced substantial mice death, which was significantly decreased by andrographolide sulfonate treatment. The elevation of inflammatory cytokines including IL-6, IL-17A, TNF-alpha as well as IFN-gamma in colonic tissues levels were decreased after administration of andrographolide sulfonate. Next, CD4(+) T cell and macrophage infiltration was found to descend. The subset of pathogenic CD4(+) T cell subset including CD4(+)IFN-gamma(+) (Th1) and CD4(+)IL-17A(+) (Th17) were also suppressed by andrographolide sulfonate. Further, the restrain of p38 and p65 activation were also observed after andrographolide sulfonate administration. Finally, TNBS-induced colonic epithelial damage as well as fibrosis were significantly mitigated by andrographolide sulfonate. Based on the results got here, we can make a conclusion that andrographolide sulfonate could decrease inflammation and epithelial damage as well as fibrosis thus ameliorating chronic colitis in mice. Our study suggest the possible use of andrographolide sulfonate for chronic colitis treatment in clinical.