The Therapeutic Effects Of Anticoagulation On Experimental Colitis Of Rats

Objective: To analyze the therapeutic effect of anticoagulation on experimental colitis of rats.Methods: 1. Rat models of experimental colitis were established by enema with 2, 4, 6-trinitrobenzenesulphonic acid (TNBS). To make sure that there if there is a hypercoagulabale state in the colitis model, we assigned rats to 3 group randomly:①Healthy control group: rats were emenaed with normal saline;②1 week colitis group: In this group rats were killed 7days after TNBS enema.③2 weeks colitis group:The rats with TNBS induced colitis were killed 14 days after enema.2. Heparin was given as a anticoagulation therapy to the TNBS induced colitis. 1)acute inflammatory stage:①Healthy control;②1 week colitis group;③1 week colitis treated with heparin:Heparin were given 400u/kg twice a day through hypodermic injection d0-d7. 2)Chronic inflammatory stage:①healthy control;②2 week colitis group;③2 weeks colitis treated with heparin: Heparin was given 400u/kg twice a day through hypodermic injection d7-d14.3. In order to identify the mechanism of the anti-inflammatory effect of the heparin, nucleoprotamine were used as antagonism of heparin. The rats were assigned to 3 groups:①2 week colitis group;②Heparin group: Heparin were given 400u/kg through peritoneal injection twice a day d0-d14;③Heparin- nucleoprotamine group: heparin and nucleoprotamine were given at the proportion of 100u:1mg through peritoneal injection twice a day d0-d14.4. We choose warfarin sodium as another anticoagulant to treat TNBS colitis model. The rats were randomly assigned to 2 groups:①Colitis group;②Warfarin therapy group: Warfarin (240ng/kg) was given by intragastric administration once a day (d7-d14).5. To compare the effects between the anticoagulation therapy and the traditional therapy we assigned rats into 5 group:①colitis group;②heparin therapy group: Heparin were given 400u/kg twice a day through hypodermic injection d7-d14.;③Warfarin sodium therapy group: Warfarin (240ng/kg) was given by intragastric administration once a day (d7-d14);④salicylazosulfapyridine (SASP) therapy group: SASP (100mg/kg) was given by intragastric administration once a day (d7-d14);⑤SASP-heparin group,heparin (400u/kg twice a day given by hypodermic injection ) combine with SASP (100mg/kg once a day given through intragastric administration d7-d14) were administratated to the rats 7 days after TNBS enema.In each group we assess the damage and inflammatory state of the colitis rats by DAI,macroscopical and histological scores in each group. We choose such coagulation index as prothrombin time (PT),activated partial thromboplastin time (APTT),prothrombin time international normalized ratio (PTINR) and the activity antithrombase (AT) to measured the state of coagulation.RESULT: 1. Compared with healthy control group 1 week colitis group and 2 weeks colitis group have a shorten APTT,PT as well as a lower activity of AT (P<0.05).2. Heparin could relief the hypercoagulabale state of the colitis rats. At the same time heparin therapy group showed us that compared with colitis group, they have lower score on the macroscopical and histological (P<0.05).3. There is no difference with statistical significance between the colitis group and the heparin- nucleoprotamine group (P>0.05).4. Compared with colitis group warfarin sodium group have a longer PT and APTT and lower score on DAI,macroscopical and histological score (P<0.05). 5. Anticoagulation therapy have similar acore on DAI,macroscopical and histological score with SASP therapy group. Compared with other group, heparin combin with SASP therapy group have a lower score on the index of inflammatory and damage (P<0.05).CONCLUSION:1. TNBS induced colitis model has a state of hypercoagulabale.2. Heparin can relieve the hypercoagulabale state induced by inflammation.3. Nucleoprotamine could rivalry heparin's anticoagulation effect as well as its anti-inflammatory effect.4. Another kind of anticoagulant-warfarin sodium can relieve the colitis induced by TNBS. This result showed us anticoagulation therapy can relieve inflammatory.5. Anticoagulation therapy has similar effect to traditional SASP therapy. The effect of heparin combine with SASP therapy is better than we use one of the two drugs alone.