蒿甲醚对DSS诱导实验性结肠炎小鼠肠纤维化的抑制作用

Inhibitory effect of artemether on colonic fibrosis in mice with colitis induced by dextran sulfate sodium

目的探讨蒿甲醚对DSS诱导的实验性结肠炎小鼠肠纤维化的影响和机制。方法将44只C57BL/6小鼠随机分为正常对照组8只、模型组、地塞米松组和蒿甲醚组各12只。对照组饮用蒸馏水,另三组用3%硫酸葡聚糖溶液替代蒸馏水建模后分别以安慰剂橄榄油、地塞米松(DXM)和蒿甲醚灌肠等处理。对比实验结束时各组小鼠临床表现、疾病活动指数(DAI)及小鼠结肠长度、结肠重量。采用HE染色和M asson染色观察小鼠结肠组织损伤和纤维化变化。检测结肠组织中转化生长因子β1水平,检测血清结缔组织生长因子、Ⅲ型前胶原的水平。结果与对照组相比,模型组小鼠体重减轻、DAI评分升高、结肠长度缩短、结肠重量显著增加(P <0.01)。模型组小鼠结肠组织大体损伤评分、组织损伤评分及胶原面积较正常对照组显著升高(P <0.01)。蒿甲醚干预后,小鼠体重、DAI评分、大体评分、组织损伤评分及胶原面积比等指标均有所改善。模型组小鼠结肠CTGF、Ⅲ型前胶原和TGF-β1mRNA含量均较地塞米松组及蒿甲醚组显著上升(P均<0.01)。结论蒿甲醚能有效抑制DSS诱导的结肠炎小鼠肠纤维化。其抗纤维化机制可能与抑制TGF-β、CTGF有关,为解决肠纤维化和肠狭窄提供一定的实验依据。

Objective To investigate the effect of artemether on colonic fibrosis in mice with colitis induced by dextran sulfate sodium（DSS） and its possible mechanism. Methods Forty-four C57BL/6 ,nice were randomly divided into normal control group （ 8 mice）, model group （ 12 mice）, dexamethasone group （ 12 mice） and mlemether group （ 12 mice）. The control group was treated with distilled water, and the other three groups were treated with placebo olive oil, dexamethasone （DXM） or artemether enema, respectively. The clinical manitestations, disease activity index （ DAI）, colon length and colon weight of each group were compared at the end of the expenment.The damage and fibrosis of colon were detected with HE staining and Masson collagen staining, respectively. Transtonning growth tactor-betal（TGF-β1） mRNA in colon tissues and connective tissue growth factor were tested. Results Compared with the control group, the weight loss, DAI score, colon length and colon weight in the model group were significantly increased （P 〈 0. 01 ）. The macroscopic and micrpscopic colonic damage scores and collagen area were significantly higher in model group than those in normal control group （ P 〈 0. 01 ）. All above parameters were improved after intervention of artemether. High levels of CTGF, PC Ⅲ and TGF- β1 were detected in model group compared with dexamethasone（DX） group and artemether group （all P values 〈 0.01） .Conclusions Artemether can effectively inhibit intestinal fibrosis induced by DSS in colitis mice. Its anti-fibrosis mechanism may be related to the inhibition of TGF-β1 and CTGF.