硫代磺胺砒啶通过抑制NF-κB信号通路调节乙酸诱导的小鼠急性结肠炎症反应  

Thio sulfonamides pyridine regulation of acute colonic inflammation in mice induced by acetic acid by inhibiting NF-kappa B signaling pathway

作　　者：何熙国 胡艺[1] HE Xi-guo, Hu Yi.(Department of C, astroenterology , Jiangyou People＇s Hospital, Jiangyou 621700, Chin)

机构地区：[1]江油市人民医院消化内科,四川江油621700

出　　处：《解剖学研究》2018年第1期58-61,共4页Anatomy Research

摘　　要：目的使用乙酸经灌肠诱导的小鼠急性结肠炎模型模拟临床溃疡性结肠炎,探究柳氮磺胺吡啶治疗结肠炎的作用机制,为临床应用提供实验基础。方法将40只C57BL/6雌性小鼠随机分为对照组、模型组和高低剂量给药组。小鼠禁食不禁水24 h,造模前使用10%水合氯醛腹腔注射麻醉小鼠,各给药组和模型组小鼠分别按0.2ml/20g体质量经肛门使用塑料导管灌肠5%乙酸生理盐水溶液,倒置30 s后,使用1 ml生理盐水冲洗肠道,对照组灌入正常生理盐水后冲洗肠道,造模后第1天高低剂量给药组分别灌胃100、200 mg/kg的柳氮磺胺吡啶,模型组和对照组给予相应的溶剂灌胃。结果柳氮磺胺吡啶治疗组较模型组能够有效地抑制结肠萎缩变短,显著提高肠质量分数(P<0.05)。给药组结肠切片在病理组织学评价能够有效地缓解结肠组织病变水平。治疗组MPO和NO水平较模型组显著下降(P<0.05)。与对照组相比,模型组小鼠血清中TNF-α、IL-1β水平显著升高(P<0.05),给药后小鼠机体炎症程度减轻。与对照组相比,模型组小鼠结肠组织中p-p65、TLR4蛋白的表达显著增加,同时P65蛋白的表达降低,表明在模型中NF-κB通路处于激活状态,与模型组比较,各给药治疗组小鼠结肠组织p-p65、TLR4蛋白显著下调,P65蛋白增加,说明柳氮磺胺吡啶可以在一定程度上抑制NF-κB通路的激活。结论本研究中使用5%乙酸生理盐水溶液经灌肠后成功诱导小鼠急性结肠炎模型,模型组小鼠炎症因子表达上升,同时NF-κB信号通路处于激活状态。柳氮磺胺吡啶灌胃治疗之后能够降低小鼠机体炎症水平,同时能够显著抑制NF-κB通路的激活,有助于治疗小鼠急性结肠炎。Objective To investigate the mechanism of sulfasalazine in the treatment of colitis by simulating elini- cal ulcerative colitis by acetic acid enema-induced acute colitis model in mice, and to provide experimental basis for clini- cal application. Methods Forty C57BL/6 female mice were randomly divided into control group, model group and high and low dose group. Mice were fasted for 24 hours, before the model before the use of 10% chloral hydrate intraperitoneal injec- tion of anesthetized mice, the administration group and model group mice were 0.2 ml/20 g body weight through the anus us- ing plastic catheter enema 5% acetic acid physiological saline Aqueous solution, inverted 30 s, the use of lml saline rinse the intestinal tract, the control group poured into the normal saline after washing the intestine, the first day after the model high and low dose group were given 100, 200 mg/kg of sulfasalazine, The model group and the control group were given the corresponding solvent gavage. Results Compared with the model group, the sulfatoxine treatment group could effectively in- hibit the colonic atrophy and significantly increase the intestinal mass fraction （P〈0.05）. The histological evaluation of co- lonic sections in the administration group can effectively relieve the level of colonic tissue lesions. The levels of MPO and NO in the treatment group were significantly lower than those in the model group （P〈0.05）. Compared with the control group, the levels of TNF-α and IL-1β in the serum of the model group were significantly higher than those in the control group （P〈 0.05 ）. Compared with the control group, the expression of p-p65 and TLR4 protein in the colon tissue of the model group was significantly increased, and the expression of P65 protein was decreased in the model group, indicating that the NF-KB pathway was activated in the model group. The expression of p-p65 and TLR4 protein in the colon tissue of mice was signifi- cantly down-regulated and the P65 protein was increased, indicati

关 键 词：乙酸 结肠炎 NF—KB信号通路 柳氮磺胺吡啶 

分 类 号：R574.62[医药卫生—消化系统]