牛磺熊去氧胆酸对DSS诱导大鼠溃疡性结肠炎的治疗作用及可能机制

Therapeutic Effect of Tauroursodeoxycholic Acid on DSS Induced Ulcerative Colitis in Rats and Its Possible Mechanism

目的:探究牛磺熊去氧胆酸(TUDCA)对DSS诱导的大鼠溃疡性结肠炎的治疗作用及可能机制。方法:选取健康成年雄性Sprague-Dawley(SD)大鼠30只,随机分为正常组、模型组、治疗组,每组10只。模型组和治疗组给予葡聚糖硫酸钠(dextran sulphate sodium,DSS)诱导大鼠溃疡性结肠炎模型。正常组和模型组给予生理盐水灌胃,治疗组给予TUDCA灌胃,治疗7 d后处死大鼠,观察大鼠的一般情况及结肠组织病理改变。比较三组DAI、HI评分。Western blot检测大鼠结肠组织GRP78、PERK、eIF2α、ATF4、CHOP蛋白表达水平。结果:治疗组大鼠一般情况及结肠组织病理情况均优于模型组。模型组、治疗组DAI评分均明显高于正常组(P<0.05),而治疗组低于模型组,差异有统计学意义(P<0.05)。模型组、治疗组HI评分均明显高于正常组(P<0.05),而治疗组低于模型组,差异有统计学意义(P<0.05)。模型组、治疗组结肠组织GRP78、PERK、eIF2α、ATF4、CHOP蛋白表达水平均明显高于正常组(P<0.05),而治疗组低于模型组,差异有统计学意义(P<0.05)。结论:TUDCA对DSS诱导的大鼠溃疡性结肠炎具有治疗作用,其机制可能是通过抑制PERK-eIF2α-ATF4-CHOP通路发挥分子生物学作用。

Objective:To explore the therapeutic effect and possible mechanism of Tauroursodeoxycholic Acid (TUDCA) on DSS induced ulcerative colitis in rats.Method:Thirty healthy adult male Sprague-Dawley (SD) rats were selected and randomly divided into the normal group,the model group and the treatment group,with 10 rats in each group.The model group and the treatment group were given Dextran Sulphate Sodium (DSS) to induce rat ulcerative colitis model.The normal group and the model group were given normal saline intragastric administration,and the treatment group was given TUDCA intragastric administration.After 7 days of treatment,the rats were sacrificed..The general condition of the rats and the pathological changes of colon tissue were observed.DAI and HI scores of the three groups were compared.Western blot was used to detect the proteins expression levels of GRP78,PERK,eIF2α,ATF4,CHOP in rat colon tissue.Result:The general condition and pathological condition of colon tissue in the treatment group were better than those in the model group.The DAI score of the model group and the treatment group was significantly higher than that of the normal group (P<0.05),while the treatment group was lower than that of the model group,the difference was statistically significant (P<0.05).The HI score of the model group and the treatment group was significantly higher than that of the normal group (P<0.05),while the treatment group was lower than that of the model group,the difference was statistically significant (P<0.05).The proteins expression levels of GRP78,PERK,eIF2α,ATF4 and CHOP in colon tissues of the model group and the treatment group were significantly higher than those in the normal group (P<0.05),while the treatment group were lower than those of the model group,the differences were statistically significant (P<0.05).Conclusion:TUDCA has a therapeutic effect on DSS induced ulcerative colitis in rats,and its mechanism may be through inhibiting the Perk-EIF2 α-ATF4-CHOP pathway.