吴茱萸碱对DSS诱导小鼠急性溃疡性结肠炎的保护作用研究

The Protective Effects Research of Evodiamine on Acute Ulcerative Colitis Induced by DSS in Mice

目的:溃疡性结肠炎是诱发炎症性相关结直肠癌的最主要病因。前期研究表明,吴茱萸碱对于氧化偶氮甲烷/葡聚糖硫酸钠诱导的小鼠炎症性相关结直肠癌有着显著的预防作用,本研究旨在探究吴茱萸碱是否在结肠炎急性阶段即可起到预防保护作用。方法:建立葡聚糖硫酸钠诱导的小鼠急性结肠炎模型,将40只小鼠随机分为溶剂对照组、模型组、吴茱萸碱低剂量组、吴茱萸碱高剂量组。观察小鼠一般活动状况,记录疾病活动指数,进行结肠大体损伤评分及组织学评分;测定结肠组织中丙二醛、超氧化物歧化酶、髓过氧化酶,炎性因子IL^-1β、IL-6、IL^-10、TGF-β1、TNF-α,氧化损伤产物8-Oxoguanine、Nitrotyrosine的表达及血清中一氧化氮含量。结果:与模型组相比,吴茱萸碱能有效地降低急性结肠炎小鼠疾病活动指数评分,减轻结肠缩短现象和葡聚糖硫酸钠所造成的结肠组织学损伤,同时降低一氧化氮、丙二醛、髓过氧化酶含量,升高总超氧化物歧化酶活性,并显著降低8-Oxoguanine、Nitrotyrosine在结肠组织中的表达,亦能显著抑制促炎因子IL^-1β,TNF-α,IL-6的分泌,促进抗炎因子TGF-β1、IL^-10的产生。结论:吴茱萸碱可通过保护肠道上皮屏障完整性,抑制炎性因子的分泌,促进抗炎因子的产生,减轻机体炎症及氧化应激来达到改善急性溃疡性结肠炎的作用,对溃疡性结肠炎急性发病阶段有着较好的治疗保护作用。

Objective:Ulcerative colitis is the most important cause of colitis-associated cancer.Previous studies have shown that evodiamine has a significant preventive effect on mice with colitis-associated cancer induced by azoxymethane(AOM)/dextran sulfate sodium(DSS).This study aims to explore whether evodiamine can play a preventive and protective role in the acute stage of colitis.Methods:The model of acute colitis in mice induced by DSS was established.Forty mice were randomly divided into vehicle control group,model group,low-dose evodiamine group and high-dose evodiamine group.The general activity and disease activity index of the mice were recorded,the colonic gross injury score and histological score were performed.The expression of malondialdehyde(MDA),superoxide dismutase(SOD),myeloperoxidase(MPO),IL^-1β,IL-6,IL^-10,TGF-β1,TNF-α,8-oxoguanine,nitrotyrosine in colonic tissue and the content of serum nitric oxide(NO)were detected.Results:Compared with the model group,evodiamine could effectively reduce the score of disease activity index in mice with acute colitis,reduce the colon shortening phenomenon and the colon histological damage caused by DSS.The contents of NO,MDA and MPO were decreased,the activity of SOD was increased,and the expressions of 8-oxoguanine and nitrotyrosine were significantly decreased.Evodiamine can significantly inhibit the secretion of pro-inflammatory factors IL^-1β,TNF-αand IL-6,and promote the production of anti-inflammatory factors TGF-β1 and IL^-10.Conclusion:Evodiamine can improve acute ulcerative colitis by protecting the integrity of intestinal epithelial barrier,inhibiting the secretion of inflammatory factors,promoting the production of anti-inflammatory factors,reducing inflammation and oxidative stress.This study confirmed that evodiamine had a better therapeutic and protective effect on acute stage of ulcerative colitis.