CAJ | 학술논문

背景:排斥反应的发生是导致小肠移植失败的主要原因,趋化因子及其受体介导的细胞免疫在急性排斥反应中具有重要作用,以趋化因子受体为靶位的治疗方案,可能为临床小肠移植的免疫治疗提供借鉴.目的:观察趋化因子RANTES(Met-RANTES)对同种异体大鼠异位小肠移植术后移植物的存活时间和组织病理学改变的影响,以及与小剂量他克莫司的协同效应.设计、时间及地点:随机数字表法区组,对照观察实验,于2003-09/2005-03在解放军第四军医大学西京医院胃肠外科实验室完成.材料:健康成年雄性大鼠180只,90只SD大鼠作为供体,90只Wistar大鼠作为受体,施行异位节段性小肠移植.方法:小肠移植后,大鼠随机分为3组,30只/组:对照组,只做异位小肠移植,不给予任何药物治疗,Met-RANTES治疗组:移植后0～7 d,腹腔注射Met-RANTES200 μg/d;Met-RANTES联合小剂量他克莫司治疗组:移植后0～7 d,腹腔注射Met-RANTES 200 μg/d+肌肉注射他克莫司0.5 mg/(kg·d).主要观察指标:观察移植大鼠的一般状况和存活时间,并于移植后第1,3,5,7天每组各处死6只大鼠,切取移植肠标本进行组织病理学检查和组间比较.结果:移植后的90只受体大鼠全部进入结果分析.对照组大鼠存活时间中位数为7.2 d(1.5),全部死于急性排斥反应及感染.组织病理学检查显示移植后第3,5,7天分别符合轻、中、重度排斥反应.Met-RANTES治疗组大鼠存活时间中位数为19.2 d(16.4),与对照组相比存活时间明显延长(P<0.01).Met-RANTES+小剂量他克莫司治疗组大鼠存活时间中位数为30.9 d(9.0),与前两组有显著差异(P<0.01).Met-RANTES治疗组和Met-RANTES+小剂量他克莫司治疗组大鼠组织病理学检查无明显排斥反应征象,可长期存活.结论:Met-RANTES能明显抑制小肠移植急性排斥反应,有效保护移植肠功能,显著延长移植物的存活时间,并可增强小剂量他克莫司的免疫抑制作用. 揹景:排斥反應的髮生是導緻小腸移植失敗的主要原因,趨化因子及其受體介導的細胞免疫在急性排斥反應中具有重要作用,以趨化因子受體為靶位的治療方案,可能為臨床小腸移植的免疫治療提供藉鑒.目的:觀察趨化因子RANTES(Met-RANTES)對同種異體大鼠異位小腸移植術後移植物的存活時間和組織病理學改變的影響,以及與小劑量他剋莫司的協同效應.設計、時間及地點:隨機數字錶法區組,對照觀察實驗,于2003-09/2005-03在解放軍第四軍醫大學西京醫院胃腸外科實驗室完成.材料:健康成年雄性大鼠180隻,90隻SD大鼠作為供體,90隻Wistar大鼠作為受體,施行異位節段性小腸移植.方法:小腸移植後,大鼠隨機分為3組,30隻/組:對照組,隻做異位小腸移植,不給予任何藥物治療,Met-RANTES治療組:移植後0～7 d,腹腔註射Met-RANTES200 μg/d;Met-RANTES聯閤小劑量他剋莫司治療組:移植後0～7 d,腹腔註射Met-RANTES 200 μg/d+肌肉註射他剋莫司0.5 mg/(kg·d).主要觀察指標:觀察移植大鼠的一般狀況和存活時間,併于移植後第1,3,5,7天每組各處死6隻大鼠,切取移植腸標本進行組織病理學檢查和組間比較.結果:移植後的90隻受體大鼠全部進入結果分析.對照組大鼠存活時間中位數為7.2 d(1.5),全部死于急性排斥反應及感染.組織病理學檢查顯示移植後第3,5,7天分彆符閤輕、中、重度排斥反應.Met-RANTES治療組大鼠存活時間中位數為19.2 d(16.4),與對照組相比存活時間明顯延長(P<0.01).Met-RANTES+小劑量他剋莫司治療組大鼠存活時間中位數為30.9 d(9.0),與前兩組有顯著差異(P<0.01).Met-RANTES治療組和Met-RANTES+小劑量他剋莫司治療組大鼠組織病理學檢查無明顯排斥反應徵象,可長期存活.結論:Met-RANTES能明顯抑製小腸移植急性排斥反應,有效保護移植腸功能,顯著延長移植物的存活時間,併可增彊小劑量他剋莫司的免疫抑製作用.
배경:배척반응적발생시도치소장이식실패적주요원인,추화인자급기수체개도적세포면역재급성배척반응중구유중요작용,이추화인자수체위파위적치료방안,가능위림상소장이식적면역치료제공차감.목적:관찰추화인자RANTES(Met-RANTES)대동충이체대서이위소장이식술후이식물적존활시간화조직병이학개변적영향,이급여소제량타극막사적협동효응.설계、시간급지점:수궤수자표법구조,대조관찰실험,우2003-09/2005-03재해방군제사군의대학서경의원위장외과실험실완성.재료:건강성년웅성대서180지,90지SD대서작위공체,90지Wistar대서작위수체,시행이위절단성소장이식.방법:소장이식후,대서수궤분위3조,30지/조:대조조,지주이위소장이식,불급여임하약물치료,Met-RANTES치료조:이식후0～7 d,복강주사Met-RANTES200 μg/d;Met-RANTES연합소제량타극막사치료조:이식후0～7 d,복강주사Met-RANTES 200 μg/d+기육주사타극막사0.5 mg/(kg·d).주요관찰지표:관찰이식대서적일반상황화존활시간,병우이식후제1,3,5,7천매조각처사6지대서,절취이식장표본진행조직병이학검사화조간비교.결과:이식후적90지수체대서전부진입결과분석.대조조대서존활시간중위수위7.2 d(1.5),전부사우급성배척반응급감염.조직병이학검사현시이식후제3,5,7천분별부합경、중、중도배척반응.Met-RANTES치료조대서존활시간중위수위19.2 d(16.4),여대조조상비존활시간명현연장(P<0.01).Met-RANTES+소제량타극막사치료조대서존활시간중위수위30.9 d(9.0),여전량조유현저차이(P<0.01).Met-RANTES치료조화Met-RANTES+소제량타극막사치료조대서조직병이학검사무명현배척반응정상,가장기존활.결론:Met-RANTES능명현억제소장이식급성배척반응,유효보호이식장공능,현저연장이식물적존활시간,병가증강소제량타극막사적면역억제작용.
BACKGROUND: Rejection is the main cause of the failure in small intestine transplantation. Cellular immunity mediated by chemotatic factor and the receptor plays an important role in acute rejection. We regard chemokine receptor as target site to design the treatment, which may provide reference for the immunotherapy in clinical small intestine transplantation. OBJECTIVE: To observe the effect of chemokine receptor antagonist, regulated upon activation, normal T cell expressed and secreted (Met-RANTES), on the survival time and histopathological changes of allograft rats which have received heterotopic small intestine transplantation, and the coordinative effects of Met-RANTES used together with low-dose tacrolimus.DESIGN, TIME AND SETTING: Randomized complete-block design and controlled animal experiment, performed in the Department of Gastrointestinal Surgery, Xijing Hospital, the Fourth Military Medical University of Chinese PLA between September 2003 and March 2005.MATERIALS: 180 healthy adult male rats including 90 rats (donors) and 90 Wistar rats (recipients) were involved in this study. Heterotopic segmental small intestine transplantation was performed.METHODS: The rats were randomly divided into 3 groups with 30 rats for each group. Control group: Rats were treated with heterotopic small intestine transplantation alone; Met-RANTES group: Rats were treated with an intraperitoneal injection of Met-RANTES (200 μg/d) at 0-7 days after transplantation; Met-RANTES+low-dose FK506 group: Rats were treated with an intraperitoneal injection of Met-RANTES (200 μg/d)+tacrolimus (0.5 mg/kg/d) at 0-7 days after transplantation.MAIN OUTCOME MEASURES: Gross status and survival time were detected; in addition, every 6 rats were sacrificed at different time points, such as 1,3, 5, and 7 days after transplantation, to compare histopathological changes. RESULTS: Following transplantation, 90 Wistar rats (recipients) were all involved in the final analysis. The survival time median in the control group was 7.2 days (1.5), and all rats died of acute rejection and infection. Histopathological examination showed that mild, moderate and severe rejections were detected at day 3, 5, and 7 after transplantation, respectively. The survival time median in the Met-RANTES group was 19.2 days (16.4), which was significantly longer than the control group (P<0.01). The survival time median in the Met-RANTES+low-dose tacrolimus group was 30.9 days (9.0), and there were significant differences in survival rate as compared with control group and Met-RANTES group (P<0.01). While the rats in the Met-RANTES group and the Met-RANTES+low-dose tacrolimus group showed no obvious indication of rejection.CONCLUSION: Met-RANTES may obviously inhibit acute rejection following small intestine transplantation, effectively protect the function of grafts, and significantly prolong the survival time of the recipients. In addition, Met-RANTES may enhance the immunosuppressive function of low-dose tacrolimus.