肝素治疗右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察

The preventive and therapeutic effects of heparin on dextran sulphate sodium-induced colitis in mice

目的 评价肝素预防及治疗右旋葡聚糖硫酸钠 (DSS)诱导小鼠结肠炎的有效性。方法 32只小鼠中 ,16只正常小鼠分成两组 ,饮用DSS 7d的同时预防组皮下注射肝素 ,对照组皮下注射生理盐水 ;另 16只饮用DSS 7d后诱导结肠炎的小鼠分成两组 ,治疗组皮下注射肝素 ,对照组皮下注射生理盐水。用疾病活动指数、组织学评分、TNF α的表达和马休斯猩红兰 (MSB)检测微血栓评价疗效。结果 肝素在预防组降低微血栓的形成 ,对照组 8只中 4只微血栓阳性 ,预防组均阴性 (P =0 .0 38)。治疗组组织学评分、TNF α的表达明显降低 ,治疗组与对照组的直肠、横结肠组织学评分和TNF α的表达分别为 1.33和 1.85 (P <0 .0 5 ) ,0 .92和 1.6 8(P <0 .0 5 ) ,(5 .5± 3.5 ) %和 (10 .8± 4.2 ) % (P <0 .0 5 )。结论 肝素可抑制DSS诱导结肠炎小鼠血栓形成和结肠炎症 。

Objective To evaluate the preventive and therapeutic effects of heparin on dextron sulphate sodium (DSS)-induced colitis in mice. Methods The normal mice (n=16) which had been received DSS orally for 7 days were randomized into two groups, the preventive group with heparin subcutaneous administration, and the control group with normal saline subcutaneous administration. The DSS-induced colitis mice (n=16) were randomized into two groups, the treatment group with heparin and the control group with normal saline subcutaneous injection for 7 days. The preventive and therapeutic effects of heparin were assessed by disease activity index (DAI), histological score, TNF-α mRNA expression using hybridization in situ, and Martius scarlet blue (MSB) fibrin staining used to identify microvascular thrombi. Results Microvascular thrombi in the prevention group significantly decreased compared with those in the controls. Microvascular thrombi were positive in 4 of 8 controls, none in the prevention group (P=0.038). Histological score and TNF-α mRNA in the treatment group significantly decreased compared with those in the controls. Histological score of rectum and transverse colon, and expression of TNF-α mRNA in the treatment group and those in the controls were 1.33 and 1.85(P< 0.05), 0.92 and 1.68 (P<0.05), and (10.8±4.2)% and ( 5.5± 3.5)%(P< 0.05) respectively.Conclusions Heparin effectively inhibits microvascular thrombosis and the colonic and rectal inflammation in the mice DSS-induced colitis in mice. These experimental results suggest that heparin might also be used effectively in ulcerative colitis.