中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2012年
3期
165-169
,共5页
王祥民%潘秀英%曾令宇%安立才%陈伟%张翠平%潘彬%徐开林
王祥民%潘秀英%曾令宇%安立纔%陳偉%張翠平%潘彬%徐開林
왕상민%반수영%증령우%안립재%진위%장취평%반빈%서개림
小鼠%造血干细胞移植%移植物抗宿主病%环孢素A%钴原卟啉
小鼠%造血榦細胞移植%移植物抗宿主病%環孢素A%鈷原卟啉
소서%조혈간세포이식%이식물항숙주병%배포소A%고원계람
Mice%Hematopoietic stem cell transplantation%Graft versus host disease%Cyclosporine%Cobalt protoporphyrin
目的 探讨应用环孢素A(CsA)联合钴原卟啉(CoPP)预防小鼠异基因造血干细胞移植(allo-HSCT)后移植物抗宿主病(GVHD)的作用.方法 以C57BL/6小鼠为供鼠,Balb/c小鼠为受鼠,分为4组:清髓性全身照射(TBI)组,受鼠TBI后经尾静脉注射磷酸盐缓冲液；常规异基因移植组(BS组),受鼠TBI后经尾静脉注射供鼠骨髓细胞与脾细胞的混合悬液(含骨髓细胞5×106个和脾细胞5×105个)；CsA组,受鼠HSCT后腹腔注射CsA;CsA联合CoPP干预组(联合组),受鼠HSCT后腹腔注射CsA和CoPP.观察受鼠存活情况,记录体重.获取受鼠肝脏、小肠和皮肤组织样本,观察GVHD的病理变化；行Masson染色,观察肾组织纤维化；检测受鼠肾组织血红素氧合酶1(HO-1)mRNA的表达.结果 与BS组和CsA组相比较,联合组GVHD程度较轻,体重下降较少且恢复较快.移植后30d时BS组累积存活率为36.8％,联合组为69.6％,CsA组为53.5％,差异有统计学意义(P＜0.05).联合组小鼠肝脏、小肠和皮肤组织可见细胞水肿、变性均较轻,坏死少见,炎症细胞浸润较少,其病理改变较BS组和CsA组轻.联合组几乎无肾间质小管纤维化,而CsA组则较明显.联合组HO-1 mRNA表达高于BS组,CsA组HO-1 mRNA表达低于前两组(P＜0.05).结论 CsA和CoPP联合应用可增强CsA抗GVHD效应,并可减轻CsA的不良反应,其机制可能与HO-1表达上调有关.
目的 探討應用環孢素A(CsA)聯閤鈷原卟啉(CoPP)預防小鼠異基因造血榦細胞移植(allo-HSCT)後移植物抗宿主病(GVHD)的作用.方法 以C57BL/6小鼠為供鼠,Balb/c小鼠為受鼠,分為4組:清髓性全身照射(TBI)組,受鼠TBI後經尾靜脈註射燐痠鹽緩遲液；常規異基因移植組(BS組),受鼠TBI後經尾靜脈註射供鼠骨髓細胞與脾細胞的混閤懸液(含骨髓細胞5×106箇和脾細胞5×105箇)；CsA組,受鼠HSCT後腹腔註射CsA;CsA聯閤CoPP榦預組(聯閤組),受鼠HSCT後腹腔註射CsA和CoPP.觀察受鼠存活情況,記錄體重.穫取受鼠肝髒、小腸和皮膚組織樣本,觀察GVHD的病理變化；行Masson染色,觀察腎組織纖維化；檢測受鼠腎組織血紅素氧閤酶1(HO-1)mRNA的錶達.結果 與BS組和CsA組相比較,聯閤組GVHD程度較輕,體重下降較少且恢複較快.移植後30d時BS組纍積存活率為36.8％,聯閤組為69.6％,CsA組為53.5％,差異有統計學意義(P＜0.05).聯閤組小鼠肝髒、小腸和皮膚組織可見細胞水腫、變性均較輕,壞死少見,炎癥細胞浸潤較少,其病理改變較BS組和CsA組輕.聯閤組幾乎無腎間質小管纖維化,而CsA組則較明顯.聯閤組HO-1 mRNA錶達高于BS組,CsA組HO-1 mRNA錶達低于前兩組(P＜0.05).結論 CsA和CoPP聯閤應用可增彊CsA抗GVHD效應,併可減輕CsA的不良反應,其機製可能與HO-1錶達上調有關.
목적 탐토응용배포소A(CsA)연합고원계람(CoPP)예방소서이기인조혈간세포이식(allo-HSCT)후이식물항숙주병(GVHD)적작용.방법 이C57BL/6소서위공서,Balb/c소서위수서,분위4조:청수성전신조사(TBI)조,수서TBI후경미정맥주사린산염완충액；상규이기인이식조(BS조),수서TBI후경미정맥주사공서골수세포여비세포적혼합현액(함골수세포5×106개화비세포5×105개)；CsA조,수서HSCT후복강주사CsA;CsA연합CoPP간예조(연합조),수서HSCT후복강주사CsA화CoPP.관찰수서존활정황,기록체중.획취수서간장、소장화피부조직양본,관찰GVHD적병리변화；행Masson염색,관찰신조직섬유화；검측수서신조직혈홍소양합매1(HO-1)mRNA적표체.결과 여BS조화CsA조상비교,연합조GVHD정도교경,체중하강교소차회복교쾌.이식후30d시BS조루적존활솔위36.8％,연합조위69.6％,CsA조위53.5％,차이유통계학의의(P＜0.05).연합조소서간장、소장화피부조직가견세포수종、변성균교경,배사소견,염증세포침윤교소,기병리개변교BS조화CsA조경.연합조궤호무신간질소관섬유화,이CsA조칙교명현.연합조HO-1 mRNA표체고우BS조,CsA조HO-1 mRNA표체저우전량조(P＜0.05).결론 CsA화CoPP연합응용가증강CsA항GVHD효응,병가감경CsA적불량반응,기궤제가능여HO-1표체상조유관.
Objective To explore prevention of cyclosporine A (CsA) combined with Cobalt protoporphyrin (CoPP) against murine graft versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods C57BL/6 (H-2Kb) mice were used as donors and BALB/c (H-2Kd) mice as recipients,which were randomly divided into 4 groups.The mice in total body irradiation group (TBI group) were lethally irradiated and injected intravenously with PBS; The mice in Allo-HSCT group (BS group) were lethally irradiated and injected intravenously with bone marrow cells and spleen cells; The mice in CsA intervention group (CsA group) were injected with CsA intraperitoneally after allo-HSCT; The mice in CsA combine with CoPP intervention group (combination group) received both CsA and CoPP intraperitoneally after alloHSCT.Recipients were monitored for condition,survival rate and weight.The liver,small intestine and skin in the recipients were gained and pathological changes of GVHD were assessed.The kidney was stained with Masson staining dye to observe the tissue fibrosis.The expression levels of renal HO-1 mRNA in the recipients were detected.Results In contrast to BS and CsA groups,GVHD degree in combination group was mild,with less reduction and quick recovery of weight.On the day 30 after HSCT,survival rate in BS group was 36.8％,and that in combination group and CsA group was 69.6％ and 53.5％ respectively (P＜0.05).In comparison with BS and CsA groups,pathological changes in combination group were mild,cellular edema and degeneration degree of the liver,small intestine and skin were slight,and few necrosis and infiltrated inflammatory cells were observed.Tubulointerstitial fibrosis hardly occurred in combination group,but it occurred in CsA group abundantly.As compared with BS group,the expression levels of HO-1 mRNA was increased in combination group,while decreased in CsA group (P＜0.05).Conclusion CsA combined with CoPP enhanced the protective effect of CsA against GVHD,moreover,CoPP could alleviate the side effects of CsA,which might be related with up-regulation of the expression levels of HO-1.
