抗凝治疗在TNBS诱导的大鼠实验性结肠炎模型中的作用
发布时间：2018-10-31 13:06
【摘要】： 目的:研究抗凝治疗在TNBS诱导的大鼠结肠炎模型中的作用。 方法:1.建立大鼠TNBS实验性结肠炎模型,并证实在TNBS模型中存在被炎症激活的高凝状态。实验分组:①正常对照组:生理盐水灌肠,1周后处死;②1周结肠炎组:TNBS灌肠,1周后处死;③2周结肠炎组:TNBS灌肠,2周后处死。 2.使用肝素对急慢性炎症期的大鼠结肠炎模型进行抗凝治疗。实验分组:(1)急性炎症期治疗实验分组:①正常对照组;②1周结肠炎组;③1周结肠炎肝素治疗组:肝素皮下注射400u/kg bid d0-d7。(2)慢性炎症期抗凝治疗,具体分组:①正常对照组;②2周结肠炎组;③2周结肠炎肝素治疗组:肝素皮下注射400u/kg bid d7-d14。 3.使用鱼精蛋白拮抗肝素的抗凝活性并观察其作用变化以进一步证明抗凝-抗炎机制的作用。实验分组:①结肠炎组;②肝素抗凝治疗组:肝素腹腔内注射400u/kg bid d0-d14;③鱼精蛋白中和肝素组,予以肝素400u/kg以及中和量的鱼精蛋白腹腔内注射bid d0-d14。 4.使用华法林钠抗凝治疗大鼠结肠炎模型。实验分组:①结肠炎组;②华法林钠抗凝组,华法林钠240ng/kg灌胃qd d7-d14。 5.抗凝治疗和常规治疗的对比,实验分组:①结肠炎组;②肝素组,肝素400u/kg皮下注射bid d7-d14;③华法林钠组华法林钠240ng/kg灌胃qd d7-d14;④SASP组,SASP 100mg/kg灌胃qd d7-d14;⑤肝素+SASP组,同时使用肝素400u/kg bid d7-d14及SASP治疗灌胃100mg/kg qd d7-d14。以上各组在处理终止日期处死,并检查凝血指标(PT、APTT、AT)以及反映炎症及损伤的指标(疾病活动指数、大体评分、病理评分)。 结果:1.1周结肠炎组和2周结肠炎组和正常对照比较APTT、PT缩短,AT活性下降(P0.05)。 2.肝素组和正常对照组PT、APTT较结肠炎组缩短而AT活性高; DAI、大体评分、病理评分分值较结肠炎组为低(P0.05)。 3鱼精蛋白拮抗肝素组的PT、APTT、AT活性、DAI、大体评分、病理评分分值与结肠炎组差别无统计学意义(P0.05)。 4.华法林钠组PT、APTT均较结肠炎组延长,DAI、大体评分、病理评分分值较结肠炎组为低(P0.05)。 5.华法林钠组、肝素组和SASP组DAI、大体评分、病理评分分值差别无统计学意义(P0.05),而SASP+肝素效果炎症和损伤指标均低于其他组(P0.05)。 结论:1.TNBS诱导的结肠炎模型中存在高凝状态。 2.肝素可以纠正这种炎症诱导的高凝状态;同时可以减轻炎症。 3.应用鱼精蛋白中和肝素的抗凝活性后其抗炎作用也消失。 4.应用另一种抗凝药华法林钠治疗结肠炎的成功说明了抗凝可以对炎症起到拮抗的作用。 5.抗凝治疗效果类似于常规SASP治疗,肝素和SASP联合治疗优于单用肝素以及SASP。
[Abstract]:Objective: to study the role of anticoagulant therapy in rat colitis induced by TNBS. Methods: 1. The experimental colitis model of TNBS in rats was established and the hypercoagulant state activated by inflammation was confirmed in TNBS model. Experimental groups: 1 normal control group: normal saline enema, 1 week later, 21 weeks colitis group: TNBS enema, 1 week later death; 32 week colitis group: TNBS enema, 2 weeks later. 2. Heparin was used to treat acute and chronic inflammatory rat colitis model. Experimental groups: (1) acute inflammatory phase treatment group: 1 normal control group, 21 weeks colitis group; Heparin treatment group: heparin subcutaneous injection of 400u/kg bid day 0-d 7. (2) chronic inflammatory stage anticoagulant treatment, specific groups: 1 normal control group, 22 weeks colitis group; 32 week colitis heparin treatment group: heparin subcutaneous injection of 400u/kg bid d7-d 14. 3. The anticoagulant activity of heparin was antagonized by protamine and its changes were observed to further prove the anticoagulation-anti-inflammatory mechanism. Experimental groups: 1 colitis group, 2 heparin anticoagulant treatment group: heparin intraperitoneal injection of 400u/kg bid day 0-d 143 protamine neutralizing heparin group, heparin 400u/kg and neutralized protamine intraperitoneal injection of bid day 0-d 14. 4. The rat model of colitis was treated with warfarin sodium anticoagulant. Experimental groups: 1 colitis group, 2 warfarin sodium anticoagulant group, warfarin sodium 240ng/kg gavage qd d 7 d 14. 5. The comparison between anticoagulant therapy and routine therapy was divided into two groups: 1 colitis group, 2heparin group, heparin 400u/kg subcutaneous injection of bid d7-d14 + 3 warfarin sodium 240ng/kg intragastric instillation of qd d7-d14; 4SASP group, SASP 100mg/kg group, qd d 7 d 14 5 heparin SASP group, and heparin 400u/kg bid d7-d14 and SASP were used to treat 100mg/kg qd 7 d 14. The blood coagulation index (PT,APTT,AT) and the index of inflammation and injury (disease activity index, gross score, pathological score) were examined. Results: APTT,PT was shorter and AT activity was lower in 1. 1 week colitis group and 2 week colitis group than in normal control group (P 0.05). 2. The PT,APTT of heparin group and normal control group was shorter than that of colitis group, but the activity of AT was higher; DAI, gross score and pathological score were lower than that of colitis group (P0.05). 3 the PT,APTT,AT activity, DAI, gross score, pathological score of protamine antagonistic heparin group were not significantly different from those of colitis group (P0.05). 4. The PT,APTT of warfarin sodium group was longer than that of colitis group, DAI, gross score and pathological score were lower than that of colitis group (P0.05). 5. The DAI, gross score and pathological score of warfarin sodium group, heparin group and SASP group were not significantly different (P0.05), while SASP heparin effect inflammation and injury index were lower than other groups (P0.05). Conclusion: hypercoagulable state exists in 1.TNBS induced colitis model. 2. Heparin can correct the hypercoagulable state induced by inflammation and alleviate inflammation at the same time. 3. The anticoagulant activity of heparin disappeared after protamine was used to neutralize the anticoagulant activity of heparin. 4. The successful use of warfarin sodium in the treatment of colitis suggests that anticoagulation can antagonize inflammation. 5. The effect of anticoagulant therapy is similar to that of conventional SASP. The combination of heparin and SASP is superior to heparin and SASP. alone.
【学位授予单位】：北京大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R574.62;R-332
本文编号：2302297
[Abstract]:Objective: to study the role of anticoagulant therapy in rat colitis induced by TNBS. Methods: 1. The experimental colitis model of TNBS in rats was established and the hypercoagulant state activated by inflammation was confirmed in TNBS model. Experimental groups: 1 normal control group: normal saline enema, 1 week later, 21 weeks colitis group: TNBS enema, 1 week later death; 32 week colitis group: TNBS enema, 2 weeks later. 2. Heparin was used to treat acute and chronic inflammatory rat colitis model. Experimental groups: (1) acute inflammatory phase treatment group: 1 normal control group, 21 weeks colitis group; Heparin treatment group: heparin subcutaneous injection of 400u/kg bid day 0-d 7. (2) chronic inflammatory stage anticoagulant treatment, specific groups: 1 normal control group, 22 weeks colitis group; 32 week colitis heparin treatment group: heparin subcutaneous injection of 400u/kg bid d7-d 14. 3. The anticoagulant activity of heparin was antagonized by protamine and its changes were observed to further prove the anticoagulation-anti-inflammatory mechanism. Experimental groups: 1 colitis group, 2 heparin anticoagulant treatment group: heparin intraperitoneal injection of 400u/kg bid day 0-d 143 protamine neutralizing heparin group, heparin 400u/kg and neutralized protamine intraperitoneal injection of bid day 0-d 14. 4. The rat model of colitis was treated with warfarin sodium anticoagulant. Experimental groups: 1 colitis group, 2 warfarin sodium anticoagulant group, warfarin sodium 240ng/kg gavage qd d 7 d 14. 5. The comparison between anticoagulant therapy and routine therapy was divided into two groups: 1 colitis group, 2heparin group, heparin 400u/kg subcutaneous injection of bid d7-d14 + 3 warfarin sodium 240ng/kg intragastric instillation of qd d7-d14; 4SASP group, SASP 100mg/kg group, qd d 7 d 14 5 heparin SASP group, and heparin 400u/kg bid d7-d14 and SASP were used to treat 100mg/kg qd 7 d 14. The blood coagulation index (PT,APTT,AT) and the index of inflammation and injury (disease activity index, gross score, pathological score) were examined. Results: APTT,PT was shorter and AT activity was lower in 1. 1 week colitis group and 2 week colitis group than in normal control group (P 0.05). 2. The PT,APTT of heparin group and normal control group was shorter than that of colitis group, but the activity of AT was higher; DAI, gross score and pathological score were lower than that of colitis group (P0.05). 3 the PT,APTT,AT activity, DAI, gross score, pathological score of protamine antagonistic heparin group were not significantly different from those of colitis group (P0.05). 4. The PT,APTT of warfarin sodium group was longer than that of colitis group, DAI, gross score and pathological score were lower than that of colitis group (P0.05). 5. The DAI, gross score and pathological score of warfarin sodium group, heparin group and SASP group were not significantly different (P0.05), while SASP heparin effect inflammation and injury index were lower than other groups (P0.05). Conclusion: hypercoagulable state exists in 1.TNBS induced colitis model. 2. Heparin can correct the hypercoagulable state induced by inflammation and alleviate inflammation at the same time. 3. The anticoagulant activity of heparin disappeared after protamine was used to neutralize the anticoagulant activity of heparin. 4. The successful use of warfarin sodium in the treatment of colitis suggests that anticoagulation can antagonize inflammation. 5. The effect of anticoagulant therapy is similar to that of conventional SASP. The combination of heparin and SASP is superior to heparin and SASP. alone.
【学位授予单位】：北京大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R574.62;R-332
【引证文献】
相关硕士学位论文 前1条
1 赵雪云;COX-2抑制剂在大鼠胰十二指肠移植缺血再灌注损伤中对P选择素和细胞间粘附分子-1的影响[D];重庆医科大学;2012年
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