低分子量肝素对三硝基苯磺酸诱发大鼠结肠炎肿瘤坏死因子α、CD62P的影响  

Effects of low molecular weight heparin on the expression of interleukin-8,CD62P and tumor necrosis factor α in trinitrobezene sulphonic acid induced colitis in rats

作　　者：韩红[1] 夏冰[1] 刘君炎[2] 

机构地区：[1]武汉大学中南医院内一科,430071 [2]武汉大学医学院免疫学教研室

出　　处：《中华消化杂志》2003年第7期418-421,共4页Chinese Journal of Digestion

基　　金：湖北省自然科学基金 (2 0 0 0 5 0 47)

摘　　要：目的　通过观察低分子量肝素对三硝基苯磺酸 (TNBS)诱发的大鼠结肠炎肿瘤坏死因子(TNF)α ,白细胞介素 (IL) 8,及CD 6 2P表达的影响 ,在一定程度上阐明肝素抗炎的分子机制。方法　4 5只SD大鼠随机分成 3组。用TNBS/乙醇灌肠制作大鼠结肠炎模型。甲组分别在灌肠前 1h及灌肠后每天 1次皮下注射低分子量肝素 (法安明 ) 15 0U/kg ,共 6d ,至第 7天减半量注射 ,第 14天停用。乙组方法同甲组 ,但注射剂量加倍为 30 0U/kg。丙组为对照组 ,用等容量生理盐水皮下注射 ,每天 1次 ,共15d。分别在制模后第 2 4小时、第 7天及第 14天 ,随机抽取每组大鼠各 5只 ,心脏取血 ,放射免疫法检测血中血小板膜表面CD6 2P分子数的变化。ELISA法测定血清IL 8含量。同时取结肠病变部位组织 ,免疫组化法分析TNFα的组织表达及镜下评定结肠黏膜损伤Fedorak积分值。结果　与对照组比较 ,无论低剂量还是高剂量治疗组 ,低分子量肝素在制模后第 2 4小时、第 7天及第 14天对CD6 2P的分子表达均无影响 (P >0 .0 5 )。对血清IL 8及TNFα的组织表达 ,高剂量治疗组至第 7天开始下降 (P <0 .0 5 ) ,第 14天显著下降 (P <0 .0 1)。对结肠黏膜损伤Fedorak积分值的影响 ,高剂量治疗组治疗至第 14天时差异有显著性 (P <0 .0 5 )。结论　在TNBS诱?Objective To observe the effects of low molecular weight heparin on interleukin-8, CD-62P and tumor necrosis factor α(TNF α) in trinitrobenzene sulphonic acid (TNBS)- induced colitis in rats and define the mechanisms of its anti-inflammatory effects. Methods Forty-five female Sprague-Dawley rats, induced to have colitis by colonic instillation of TNBS, were divided randomly into three groups. Fifteen rats in group A were given heparin at the dose of 150 U/kg through subcutaneous injection one hour before and six days after the production of colitis. A half dose of heparin was also given for subsequent seven days. The way of the treatment of fifteen rats in group B was the same as in group A, but the dosage of heparin was twice as much as in group A. Fifteen rats in control group received the same volume of saline instead of heparin once a day. Rats in each group were sacrificed with anesthesia at the 24th hour, the 7th day and the 14th day after induction of colitis. Blood and colonic tissue of rats were collected. The expression of CD62P (P-Selectin) on the surface of blood platelet was detected using radioimmunoassay. The level of serum IL-8 was detected by ELISA. The expression of TNFα in colonic mucosa was assessed by immunohistochemistry. Results Compared with that in control group, low molecular weight heparin has no effect on the expression of CD62P ( P >0.05). The level of serum IL-8 and expression of TNF α in the colonic mucosa decreased at the 7th day ( P <0.05) and even more significantly at the 14th day in the higher dose group ( P <0.01). Effects of low molecular weight heparin on histological inflammatory grading score decreased significantly at the 14th day in the higher dose group ( P <0.05). Conclusions Low molecular weight heparin has anti-inflammatory effects through down-regulated expressions of IL-8 and TNFα, but no effect on adhesion molecular CD62P at the regular anti-coagulation dose. Low molecular weight heparin helps to protect colonic mucosae during TNBS-induced colitis in rats.

关 键 词：低分子量肝素 三硝基苯磺酸 诱发 大鼠 结肠炎 肿瘤坏死因子Α 细胞粘附分子 白细胞介素 

分 类 号：R574.62[医药卫生—消化系统] R973.2[医药卫生—内科学]