肝素对TNBS诱导的大鼠结肠炎的治疗作用及其机制  

Therapeutic Effect of Heparin on TNBS-induced Colitis in Rats and its Mechanism

作　　者：彭涛[1] 刘玉兰[1] 

机构地区：[1]北京大学人民医院消化科

出　　处：《胃肠病学》2010年第6期335-338,共4页Chinese Journal of Gastroenterology

摘　　要：背景：活动期炎症性肠病（IBD）往往伴有高凝状态，高凝状态与炎症之间的关系尚未完全明确。目的：探讨三硝基苯磺酸（TNBS）诱导的大鼠结肠炎模型中凝血异常与炎症的关系以及肝素的治疗作用及其机制。方法：40只Sprague—Dawlev大鼠分为正常对照组、结肠炎组、肝素治疗组和肝素＋鱼精蛋白组。后三组以TNBS诱导结肠炎模型，行疾病活动指数（DAI）、大体和组织病理学评分，检测血清肿瘤坏死因子（TNF）-α水平、凝血酶原时间（PT）、激活部分促凝血酶原激酶时间（APTT）、抗凝血酶（AT）活性和血小板计数。结果：与正常对照组相比，结肠炎组DAI、大体评分和组织病理学评分以及血清TNF-α．水平显著增高（P〈0．05），胛、APTT、AT活性均显著降低（P〈0．05），血小板计数显著增高（P〈0．05）。经肝素治疗后，上述指标均显著改善（P〈0．05）。肝素＋鱼精蛋白组各指标与结肠炎组无明显差异。结论：TNBS诱导的结肠炎模型中存在凝血异常，肝素可有效控制炎症激活的凝血异常．其抗炎机制可能与抗凝活性相关。鱼精蛋白可中和肝素的抗凝活性同时终止其抗炎作用。Background： Hypercoagulable state is common during the active stage of inflammatory bowel disease （[BD）, the relationship between hypereoagulation and inflammation remains unclear. Aims： To study the relationship between coagulation and inflammation in trinitrobenzenesulfonic acid （TNBS）-induced colitis as well as the therapeutic effect and mechanism of heparin on colitis in rat model. Methods： Forty Sprague-Dawley rats were randomly divided into normal control group, colitis group, heparin group and heparin＋ protamine group. Colitis was induced by TNBS in the latter three groups. Disease activity index （DAI）, macroscopic score, histopathologic score, serum TNF-α level, prothrombin time （PT）, activated partial thromboplastin time （APTT）, antithrombin （AT） activity and blood platelet count were determined. Results： Compared with normal control group, DAI, macroscopic score, histopathologic score and serum TNF-α level in colitis group were significantly increased, PT, APTT and AT activity were significantly decreased （P〈0.05）, and blood platelet count was significantly increased （P〈0.05）. After treatment with heparin, all the above-mentioned indices were significantly ameliorated （P〈0.05）. No significant differences were found between colitis group and heparin＋ protamine group. Conclusions： Abnormality of coagulation is observed in colitis induced by TNBS, and heparin is effective in controlling the coagulation abnormality activated by inflammation. The anti-inflammatory mechanism of heparin is probably related with its anticoagulation activity. Protamine can neutralize the anticoagulation activity of heparin and at the same time it ceases the anti-inflammatory effect.

关 键 词：炎症性肠病 三硝酸苯磺酸 肝素 鱼精蛋白类 

分 类 号：R574.62[医药卫生—消化系统]