低分子量肝素对实验性小鼠结肠炎的治疗作用及其机制初探  

Therapeutic Effect and Mechanism of Low Molecular Weight Heparin in Experimental Colitis in Mice

作　　者：王显飞[1] 戴俊臣[2] 陈颖萍[1] 黄旻[1] 陈村龙[3] 王霞[3] 陈烨[3] 

机构地区：[1]川北医学院附属医院消化内科,637000 [2]四川省眉山市人民医院功能科 [3]南方医科大学南方医院消化病研究所

出　　处：《胃肠病学》2010年第2期90-94,共5页Chinese Journal of Gastroenterology

摘　　要：背景：肝素具有抗凝和抗炎的双重作用，但其抗炎机制仍不明确。目的：通过观察低分子量肝素对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎结肠黏膜Syndecan-1（Sdc—1）mRNA和蛋白表达以及白细胞介素（IL）-1β mRNA表达的影响，在一定程度上阐明低分子量肝素抗炎的分子机制。方法：54只C57BL／6小鼠分为正常对照组、模型组和治疗组。小鼠饮用3％DSS溶液5d后改饮用蒸馏水2周，建立急性结肠炎慢性化模型，治疗组皮下注射低分子量肝素。实验第5、12、19d分别处死6只小鼠。行组织学评分，以RT—PCR法检测结肠黏膜Sdc-1、IL—1β mRNA表达，以免疫组化法检测结肠黏膜Sdc-1蛋白表达。结果：与正常对照组相比，模型组各时间点组织学评分、IL—1β mRNA表达显著升高（P〈0．05），Sdc—1 mRNA和蛋白表达显著降低（P〈0．05）。经低分子量肝素治疗后，上述各指标明显改善。结论：在DSS诱导的小鼠急性结肠炎慢性化过程中，低分子量肝素可能通过下调炎症介质IL-1β表达而起抗炎作用，并可能通过替代从细胞表面丢失的Sdc-1而加速修复过程，促进结肠炎的愈合。Background： Besides its well-known anticoagulant action, heparin also has anti-inflammatory effect. However, the mechanism responsible for the anti-inflammatory effect is not yet fully elucidated. Aims： To observe the effect of low molecular weight heparin （LMWH） on mRNA and protein expressions of Syndecan-1 （Sdc-1） and mRNA expression of interleukin （IL）-1β in colitis model induced by dextran sulfate sodium （DSS） in mice, and to define the mechanism of its anti-inflammatory effect. Methods： Fifty-four C57BL/6 mice were divided into normal control group, model group and treatment group. Mice were fed with 3% DSS solution for 5 days followed by distilled water for 2 weeks to induce the colitis model which progressed from acute to chronic inflammation. Mice in treatment group were given LMWH by subcutaneous injection. The mice were killed on 5th, 12th and 19th day, and the colonic histopathological score was evaluated. The mRNA expressions of Sdc-1 and IL-1β in colonic mucosa were assessed by RT-PCR. The protein expression of Sdc-1 in colonic mucosa was evaluated by immunohistochemistry. Results： Compared with the normal control group, the colonic histopathological score and mRNA expression of IL-1β at various time points were significantly increased （P〈0.05）, while mRNA and protein expressions of Sdc-1 were significantly decreased （P〈0.05） in model group. After treatment with LMWH, all the above-mentioned indices were significantly ameliorated. Conclusions： In the process of acute colitis progressing to chronic stage induced by DSS in mice, LMWH has an anti-inflammatory effect, which may be due to the down-regulation of expression of IL-1β. The administration of LMWH can reduce intestinal mucosal injury, and may replace the lost Sdc-1 from cell surface, thus speeding up the restoration process and promoting healing of colitis.

关 键 词：肝素 低分子量 结肠炎 多配体蛋白聚糖1 白细胞介素1Β 

分 类 号：R574.62[医药卫生—消化系统]