华法林钠治疗大鼠实验性结肠炎的作用

The therapeutic effects of warfarin on experimental colitis in rats

目的探讨炎症性肠病中凝血异常与炎性反应的关系。明确华法林钠抗凝治疗在2，4，6-三硝基苯磺酸钠（TNBS）诱导的实验性大鼠结肠炎模型中的作用。方法40只大鼠均分为正常对照组、结肠炎组、华法林钠组和柳氮磺胺吡啶（SASP）组，正常对照组予以0．9％氯化钠溶液灌肠，其余三组予以含有20mgTNBS的50％乙醇溶液0．5ml灌肠。造模后第7天，华法林钠组给予华法林钠溶液240ng·kg^-1·d^-1灌胃；SASP组给予SASP溶液100mg·kg^-1·d^-1灌胃；正常对照组和结肠炎组予以每天1次0．9％氯化钠溶液灌胃。第14天取大鼠血液和结肠后处死。比较各组大鼠疾病活动指数（DAI）、大鼠结肠大体评分、结肠组织病理评分、血清肿瘤坏死因子（TNF）浓度、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、血小板计数（PLT）和抗凝血酶活性（AT）值。结果第14天华法林钠组和SASP组DAI值分别为1．20±0．45和1．78±0．90，均较结肠炎组（2．25±0．89）降低，但差异均无统计学意义（P值均〉0．05）。华法林钠组和SASP组大体评分分别为1．40±0．55和3．14±1．46，均低于结肠炎组（4．75±1．66，P值均〈0．01）；而华法林钠组更低于SASP组（P〈0．01）。病理评分华法林钠组和SASP组分别为4．00±1．41和4．28±1.49，与结肠炎组比较差异有统计学意义（7．75±1．04，P值均〈0．01）。血清TNF-α正常对照组较其余三组低（P〈0．01），而结肠炎组较其余三组高（P〈0．01）。结肠炎组PT、APTT较华法林钠组和正常对照组缩短，AT活性也较后两组低（P值均〈0．01）。结肠炎组血小板计数明显高于正常对照组、SASP组和华法林钠组（P值均〈0．01）。结论TNBS诱导的大鼠结肠炎模型中存在凝血异常。华法林钠治疗可减轻实验性大鼠结肠炎的炎症和损伤水平。

Objective To study the relationship between coagulation and inflammatory in 2,4,6 trinitrobenzenesulfonate （TNBS） induced colitis model as well as the therapeutic effect of warfarin. Methods Forty SD-rats were divided into 4 groups,including normal control group （received 0.9 HCl solution）, colitis group, warfarin treated group （240 ng/kg daily） and salicylazosulfapyridine （SASP） treated group （100 mg/kg daily）. The animal model was induced by injection with 20 mg TNBS. The blood and colon of the rats were removed and the rats was sacrificed at the 14th day. The index of coagulation such as prothrombin time （PT）, activated partial thromboplastin time （APTT） and the activity of antithrombins （AT） and the level of tumor necrosis factor-α （TNF-α） were tested. The damage and inflammatory state of the colitis were evaluated by macroscopical score and histological score . The value of disease activity index （DAI） and the platelet counts were also measured. Results The value of DAI was lower in warfarin （1.20±0.45） and SASP （1.78±0.90） treated groups as compared with colitis group （2. 25 ± 0. 89 ） with no difference （ P 〉 0. 05 ）. The macroscopical score was lower in warfarin （1.40±0.55） and SASP （3. 14± 1.46） treated groups as compared with colitis group （4.75 ± 1.66, P〈0.01）. The histological score in warfarin （4.00 ± 1.41） and SASP （4.28 ±1. 49） treated groups were lower than that in colitis group （7. 75 ± 1. 04, P〈 0.01）. The level of TNF-α was lowest in normal control group （P〈0. 01）, and highest in colitis group. （P〈0.01）. The PT and APTT were shorter and the activity of AT was lower in colitis group in comparison with warfarin treated group and normal control group （P〈0.01）. The platelet counts was highest in colitis group. P〈0. 01）. Conclusion The abnormal coagulation in TNBS induced colitis can be effectively treated with warfarin.