1,25-(OH)_2D_3对DSS诱导的慢性结肠炎小鼠炎症反应的影响  

EFFECT OF 1,25-DIHYDROXYVITAMIN D3 ON INFLAMMATORY RESPONSE IN MICE WITH CHRONIC ULCERATIVE COLITIS INDUCED BY DSS

作　　者：李晨晨[1] 孙睿森 杨雯[1] 李秀花[1] 邱服斌[1] 

机构地区：[1]山西医科大学公共卫生学院,太原030001

出　　处：《营养学报》2017年第1期55-59,共5页Acta Nutrimenta Sinica

基　　金：山西省基础研究计划项目(No.2014011044-1);国家自然科学基金项目(No.81573156)

摘　　要：目的探究不同剂量1,25-(OH)_2D_3对慢性溃疡性结肠炎小鼠炎症反应TLR4信号通路中相关因子的影响。方法 9w龄雌性C57BL/6小鼠50只,适应性喂养1w后,随机分为正常组、模型组、低、中、高剂量干预组。正常组小鼠在整个实验期间自由饮用蒸馏水,其余四组在第1~7 d、15~21 d自由饮3%的DSS溶液,其余时间自由饮用蒸馏水。在实验的第15~28日,低、中、高剂量干预组小鼠每天分别灌胃含10、50、100 ng 1,25-(OH)_2D_3 0.1ml的橄榄油,正常组和模型组小鼠则只灌胃0.1ml的橄榄油。于第29日处死全部小鼠。根据小鼠的一般情况,结合结肠大体形态评分以及结肠组织病理学评分对小鼠结肠严重程度进行评估。酶联免疫吸附法检测小鼠血清TNF-α、IL-10含量,免疫组化法检测小鼠结肠组织中VDR、TLR4、TRAF6及NF-κB1蛋白含量。结果与模型组小鼠相比,低、中、高剂量1,25-(OH)_2D_3干预组小鼠结肠大体形态和组织病理学评分均低于模型组,结肠长度均长于模型组。干预后,血清TNF-α含量降低,IL-10含量有所升高,结肠组织TLR4、NF-κB1、TRAF6表达减少,VDR蛋白表达增加。结论补充1,25-(OH)_2D_3可降低结肠组织TLR4、TRAF6、NF-κB1的表达,改善慢性溃疡性结肠炎,这可能与TLR4信号通路有关。Objective To explore the effect t of 1,25-dihydroxyvitamin D3 （1,25-（OH）2D3） on inflammatory factors in TLR4 signaling pathway in mice with chronic ulcerative colitis induced by DSS.Methods Fifty 9-week-old C57BL/6 female mice were randomly divided into five groups after acclimatization for one week： normal group, model group, 10ng, 50ng and 100ng 1,25-（OH）2D3 groups. The normal group was treated with distilled water throughout the experiment, while the rest groups were exposed to dextran sodium sulfate （DSS） （3%） from the 1st to 7th day and 15th to 21st day and distilled water in the rest days. The three intervention groups were gavaged respectively with 10ng, 50ng or100ng 1,25-（OH）2D3 dissolved in 0.1 ml olive oil per mouse per day from days 15 to 28. Meanwhile, the normal group and the model group were gavaged with 0.1ml olive oil per mouse per day. All the mice were sacrificed on day 29. The severity of the colitis were evaluated by observing the changes using the macroscopic and histological scores of colon and the general conditions. ELISA was used for measuring TNF-α, IL-10 in serum. The protein expression of TLR4,TRAF6,NF-κB1 and VDR in colonic tissues were measured by immunohistochemistry.Results Compared to the model group, the 1,25-（OH）2D3 groups were lower in macroscopic and histological scores of colons, and the length of the colon was longer. In the three intervention groups, serum TNF-α and the TLR4 in the colon as well as TRAF6, NF-κB1 were downregulated, while serum IL-10 and VDR in the colon were increased.Conclusion 1,25-（OH）2D3 ameliorates colonic inflammation in DSS-induced chronic ulcerative colitis in mice through downregulating the expression of TLR4 and related cytokines, which indicates that the action may be associated with TLR4 signaling.

关 键 词：1 25-(OH)2D3 慢性溃疡性结肠炎 TLR4 TRAF6 NF-κB1 

分 类 号：R574.62[医药卫生—消化系统]