肝素治疗在三硝基苯磺酸诱导的结肠炎模型中的作用

The therapeutic effects of heparin on TNBS-induced rat colitis model

目的探讨三硝基苯磺酸（TNBs）诱导的大鼠实验性结肠炎模型中凝血异常与炎症的关系。方法将40只sD大鼠分为4组：正常对照组、结肠炎组、肝素治疗组和柳氮磺吡啶（sAsP）治疗组。检测各组的PT、APTT、抗凝血酶（AT）活性，及组织大体评分和病理评分、血中TNFα水平，并对结果进行统计学分析。结果TNBs诱导的结肠炎模型中PT及APTF均比正常对照组缩短[（14．83±0．45）s比（16．68±1．08）s及（12．49±1．30）s比（29．06±1．60）s，P值均〈0．05]，AT活性较正常对照组下降[（111．33±8．50）％比（122．13±3．52）％，P〈0．05]。肝素治疗组的阿及AFIT均较结肠炎组延长[（17．83±0．78）s比（14．83±0．45）s及（53．34±9．49）s比（12．49±1．30）s，P值均〈0．05]，AT活性较结肠炎组为高[（131．67±6．92）％比（111．33±8．50）％，P〈0．05]。sAsP治疗组与结肠炎组比较，PT和APTT差别无统计学意义（P〉0．05），AT活性较结肠炎组高[（122．33±5．82）％比（111．33±8．50）％，P〈0．05]。肝素治疗组大体评分低于结肠炎组（2．50±0．55比4．75±1．16，P〈0．05），组织病理评分明显低于结肠炎组（3．83±0．41比7．75±1．04，P〈0．05），TNFα水平比结肠炎组减低[（84．75±18．03）ng／L比（149．93±23．52）ng／L，P〈0．05]。结论TNBs诱导的实验性结肠炎模型中存在凝血异常；肝素治疗TNBs诱导的实验性结肠炎模型有效。这提示凝血系统异常在实验性结肠炎发生发展中可能起到一定作用。

Objective To study the relationship between coagulation abnormal and inflammatory in the TNBS induced rats colitis model as well as the therapeutic effect of heparin on this model. Methods Forty SD-rats were separated into 4 groups randomly, including normal control group, colitis group, heparin group and SASP group. PT, APTT and the activity of antithrombin （AT）were chosen as indexs of coagulation. The level of damage and inflammatory state of the colitis rats were assessed by macroscopical score, histological score and the level of TNFα in each group. Results Compared with normal control group, TNBS induced colitis group has a shorter PT [ （ 14. 83 ± 0. 45 ） s vs （ 16. 68 ± 1.08 ） s, P 〈 0. 05 ] and APTT[ （ 12. 49 ± 1.30） s vs （29. 06 ± 1.60） s, P 〈0. 05 ] and a lower activity level of AT [ （ 111.33± 8.50）% vs （122. 13 ±3.52）% ,P〈0.05]. In heparin group, PT,APTT were prolonged [PT： （17.83 ± 0.78）s vs （14.83 ±0.45）s,P〈0.05, APTT：（53.34 e9.49）s vs （12.49 ± 1.30）s,P〈0.05] and AT activity was higher than colitis group [ （ 131.67 ±6. 92）% vs （ 111.33±8.50）% ,P 〈0. 05]. SASP group has a similar data in PT, APTT compared with colitis group and no statistical significance（P 〉0.05）. The activity of AT in SASP group is higher than in colitis group [ （ 122. 33 ± 5.82 ） % vs （ 111.33 ± 8.50） %, P 〈0. 05]. The heparin therapy group showed lower macroscopical score（2. 50±0. 55 vs 4. 75± 1.16, P 〈 0. 05） , histological scores（3.83 ± 0. 41 vs 7.75 ± 1.04, P 〈 0. 05 ） and the level of TNFα [ （ 84. 75 ± 18.03） ng/L vs （ 149.93 ± 23.52 ） ng/L, P 〈 0. 05 3 compared with the colitis group. Conclusion Coagulation was abnormality in the rat colitis model induced by TNBS; heparin therapy is effective in the colitis model. It seemed that the abnormality of coagulation plays an important role in the pathogenesis of the rat colitis model.