抗凝治療在TNBS誘導(dǎo)的大鼠實(shí)驗(yàn)性結(jié)腸炎模型中的作用
發(fā)布時(shí)間：2018-10-31 13:06
【摘要】： 目的:研究抗凝治療在TNBS誘導(dǎo)的大鼠結(jié)腸炎模型中的作用。 方法:1.建立大鼠TNBS實(shí)驗(yàn)性結(jié)腸炎模型,并證實(shí)在TNBS模型中存在被炎癥激活的高凝狀態(tài)。實(shí)驗(yàn)分組:①正常對照組:生理鹽水灌腸,1周后處死;②1周結(jié)腸炎組:TNBS灌腸,1周后處死;③2周結(jié)腸炎組:TNBS灌腸,2周后處死。 2.使用肝素對急慢性炎癥期的大鼠結(jié)腸炎模型進(jìn)行抗凝治療。實(shí)驗(yàn)分組:(1)急性炎癥期治療實(shí)驗(yàn)分組:①正常對照組;②1周結(jié)腸炎組;③1周結(jié)腸炎肝素治療組:肝素皮下注射400u/kg bid d0-d7。(2)慢性炎癥期抗凝治療,具體分組:①正常對照組;②2周結(jié)腸炎組;③2周結(jié)腸炎肝素治療組:肝素皮下注射400u/kg bid d7-d14。 3.使用魚精蛋白拮抗肝素的抗凝活性并觀察其作用變化以進(jìn)一步證明抗凝-抗炎機(jī)制的作用。實(shí)驗(yàn)分組:①結(jié)腸炎組;②肝素抗凝治療組:肝素腹腔內(nèi)注射400u/kg bid d0-d14;③魚精蛋白中和肝素組,予以肝素400u/kg以及中和量的魚精蛋白腹腔內(nèi)注射bid d0-d14。 4.使用華法林鈉抗凝治療大鼠結(jié)腸炎模型。實(shí)驗(yàn)分組:①結(jié)腸炎組;②華法林鈉抗凝組,華法林鈉240ng/kg灌胃qd d7-d14。 5.抗凝治療和常規(guī)治療的對比,實(shí)驗(yàn)分組:①結(jié)腸炎組;②肝素組,肝素400u/kg皮下注射bid d7-d14;③華法林鈉組華法林鈉240ng/kg灌胃qd d7-d14;④SASP組,SASP 100mg/kg灌胃qd d7-d14;⑤肝素+SASP組,同時(shí)使用肝素400u/kg bid d7-d14及SASP治療灌胃100mg/kg qd d7-d14。以上各組在處理終止日期處死,并檢查凝血指標(biāo)(PT、APTT、AT)以及反映炎癥及損傷的指標(biāo)(疾病活動指數(shù)、大體評分、病理評分)。 結(jié)果:1.1周結(jié)腸炎組和2周結(jié)腸炎組和正常對照比較APTT、PT縮短,AT活性下降(P0.05)。 2.肝素組和正常對照組PT、APTT較結(jié)腸炎組縮短而AT活性高; DAI、大體評分、病理評分分值較結(jié)腸炎組為低(P0.05)。 3魚精蛋白拮抗肝素組的PT、APTT、AT活性、DAI、大體評分、病理評分分值與結(jié)腸炎組差別無統(tǒng)計(jì)學(xué)意義(P0.05)。 4.華法林鈉組PT、APTT均較結(jié)腸炎組延長,DAI、大體評分、病理評分分值較結(jié)腸炎組為低(P0.05)。 5.華法林鈉組、肝素組和SASP組DAI、大體評分、病理評分分值差別無統(tǒng)計(jì)學(xué)意義(P0.05),而SASP+肝素效果炎癥和損傷指標(biāo)均低于其他組(P0.05)。 結(jié)論:1.TNBS誘導(dǎo)的結(jié)腸炎模型中存在高凝狀態(tài)。 2.肝素可以糾正這種炎癥誘導(dǎo)的高凝狀態(tài);同時(shí)可以減輕炎癥。 3.應(yīng)用魚精蛋白中和肝素的抗凝活性后其抗炎作用也消失。 4.應(yīng)用另一種抗凝藥華法林鈉治療結(jié)腸炎的成功說明了抗凝可以對炎癥起到拮抗的作用。 5.抗凝治療效果類似于常規(guī)SASP治療,肝素和SASP聯(lián)合治療優(yōu)于單用肝素以及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.
【學(xué)位授予單位】：北京大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R574.62;R-332
本文編號：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.
【學(xué)位授予單位】：北京大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R574.62;R-332
【引證文獻(xiàn)】
相關(guān)碩士學(xué)位論文 前1條
1 趙雪云;COX-2抑制劑在大鼠胰十二指腸移植缺血再灌注損傷中對P選擇素和細(xì)胞間粘附分子-1的影響[D];重慶醫(yī)科大學(xué);2012年
，本文編號：2302297
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