中华胃肠外科杂志
中華胃腸外科雜誌
중화위장외과잡지
CHINESE JOURNAL OF GASTROINTESTINAL SURGERY
2010年
1期
60-63
,共4页
宋京海%伊藤寿记%韦军民%黄美雄
宋京海%伊籐壽記%韋軍民%黃美雄
송경해%이등수기%위군민%황미웅
FTY720%小肠移植%移植物抗宿主病%细胞凋亡%免疫调节药物
FTY720%小腸移植%移植物抗宿主病%細胞凋亡%免疫調節藥物
FTY720%소장이식%이식물항숙주병%세포조망%면역조절약물
FTY720%Small bowel transplantation%Graft versus host disease%Apoptosis%Immunosuppressant
目的 探讨免疫调节药物FTY720对小肠移植后急性移植物抗宿主病(GVHD)的治疗效果及其作用机制.方法 应用Wistar-Furth(WF)大鼠作为供体,WF和ACI大鼠的子代(F1)作为受体,同种异基因异位全小肠移植的技术方法建立GVHD的动物模型.移植受体分为实验组和对照组,每组6只.实验组从移植手术当日开始予以FTY720治疗,持续14 d;对照组在相同的时间段口服蒸馏水.术后第15天,提取受体靶器官肝脏、小肠及移植物小肠的淋巴细胞,应用免疫组织化学(免疫组化)TUNEL法和流式细胞仪检测两组淋巴细胞凋亡的变化.结果 对照组大鼠术后均死亡于GVHD,平均生存时间(16.0±1.7)d,实验组大鼠均长期成活超过100 d,两组差异具有统计学意义(P<0.01).免疫组化TUNEL法检测结果显示,实验组肝脏和移植物小肠黏膜的淋巴细胞凋亡比率均明显高于对照组,差异具有统计学意义(P<0.05).流式细胞技术分析结果显示,实验组大鼠移植物小肠黏膜内凋亡的淋巴细胞百分比为19.4%,明显高于对照组的11.8%(P<0.05);而肝脏凋亡的淋巴细胞百分比两组差异无统计学意义(P>0.05).结论 FTY720可能通过诱导淋巴细胞的凋亡,减少和抑制GVHD对靶器官的损害,改善移植大鼠的预后.
目的 探討免疫調節藥物FTY720對小腸移植後急性移植物抗宿主病(GVHD)的治療效果及其作用機製.方法 應用Wistar-Furth(WF)大鼠作為供體,WF和ACI大鼠的子代(F1)作為受體,同種異基因異位全小腸移植的技術方法建立GVHD的動物模型.移植受體分為實驗組和對照組,每組6隻.實驗組從移植手術噹日開始予以FTY720治療,持續14 d;對照組在相同的時間段口服蒸餾水.術後第15天,提取受體靶器官肝髒、小腸及移植物小腸的淋巴細胞,應用免疫組織化學(免疫組化)TUNEL法和流式細胞儀檢測兩組淋巴細胞凋亡的變化.結果 對照組大鼠術後均死亡于GVHD,平均生存時間(16.0±1.7)d,實驗組大鼠均長期成活超過100 d,兩組差異具有統計學意義(P<0.01).免疫組化TUNEL法檢測結果顯示,實驗組肝髒和移植物小腸黏膜的淋巴細胞凋亡比率均明顯高于對照組,差異具有統計學意義(P<0.05).流式細胞技術分析結果顯示,實驗組大鼠移植物小腸黏膜內凋亡的淋巴細胞百分比為19.4%,明顯高于對照組的11.8%(P<0.05);而肝髒凋亡的淋巴細胞百分比兩組差異無統計學意義(P>0.05).結論 FTY720可能通過誘導淋巴細胞的凋亡,減少和抑製GVHD對靶器官的損害,改善移植大鼠的預後.
목적 탐토면역조절약물FTY720대소장이식후급성이식물항숙주병(GVHD)적치료효과급기작용궤제.방법 응용Wistar-Furth(WF)대서작위공체,WF화ACI대서적자대(F1)작위수체,동충이기인이위전소장이식적기술방법건립GVHD적동물모형.이식수체분위실험조화대조조,매조6지.실험조종이식수술당일개시여이FTY720치료,지속14 d;대조조재상동적시간단구복증류수.술후제15천,제취수체파기관간장、소장급이식물소장적림파세포,응용면역조직화학(면역조화)TUNEL법화류식세포의검측량조림파세포조망적변화.결과 대조조대서술후균사망우GVHD,평균생존시간(16.0±1.7)d,실험조대서균장기성활초과100 d,량조차이구유통계학의의(P<0.01).면역조화TUNEL법검측결과현시,실험조간장화이식물소장점막적림파세포조망비솔균명현고우대조조,차이구유통계학의의(P<0.05).류식세포기술분석결과현시,실험조대서이식물소장점막내조망적림파세포백분비위19.4%,명현고우대조조적11.8%(P<0.05);이간장조망적림파세포백분비량조차이무통계학의의(P>0.05).결론 FTY720가능통과유도림파세포적조망,감소화억제GVHD대파기관적손해,개선이식대서적예후.
Objective To investigate the effect and mechanism of FTY720 on acute graft versus host disease (GVHD) in rat small bowel transplantation (SBTx).Methods Heterotopic SBTx was performed using a parent (WF)-into-F1 (WFxACI)rat combination.Recipient rats were divided into experimental group (n=6) and control group(n=6).Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days.Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation.Recipient survival and lymphocyte apoptosis were compared between the two groups.Results Recipients in the control group died of GVHD after a mean survival time of (16±2.1) days.FTY720-treated recipients had a significantly longer survival (>100 days).After administration of FTY720,the percentage of apoptotic lympbocytes was significantly increased in the graft as compared to that in the control group by flow cytometry.The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL.Conclusion FTY720 effectively induces the lymphocyte apoptosis,inhibits the lesion of target tissues by GVHD,and prolongs the recipient survival.