CAJ | 학술논문

目的探讨硼替佐米对小鼠急性移植物抗宿主病(aGVHD)的抑制作用及其可能机制.方法以C57BL/6小鼠为供鼠,获取骨髓细胞及脾细胞.以Balb/c小鼠为受鼠,共分为5组:空白对照组(n=17)小鼠不予任何处理;单纯照射组(n=17)小鼠仅接受7.0 Gy X射线全身照射(TBI);药物对照组(n=17)小鼠也接受TBI,并且由尾静脉注射硼替佐米;aGVHD组(n=8)小鼠TBI后注射供鼠骨髓细胞及脾细胞;实验组(n=8)小鼠TBI后输注供鼠骨髓细胞及脾细胞,并予以硼替佐米.观察各组小鼠aGVHD的发生情况、存活时间及嵌合状态,蛋白印迹法测定空白对照组、单纯照射组和药物对照组小鼠肝脏及小肠组织细胞核中核因子κB(NF-κB)p65的表达.结果 aGVHD组和实验组的临床aGVHD评分分别为7.37±0.32和5.85±0.40,实验组明显低于aGVHD组(P＜0.05).aGVHD组受鼠肝脏、小肠及皮肤组织为Thomas GVHD病理分级Ⅲ～Ⅳ级改变.实验组受鼠肝脏、小肠及皮肤组织为Ⅰ～Ⅲ级GVHD改变,较aGVHD组有所减轻.实验组存活时间长于aGVHD组(P＜0.05).aGVHD组和实验组小鼠移植后12 d时外周血细胞中H-2Kb分子阳性细胞的百分率均＞90%.药物对照组肝脏及小肠组织细胞核内NF-κB p65表达均高于单纯照射组(P＜0.05).结论硼替佐米可能通过在一定程度上抑制照射预处理损伤所致肝脏及小肠组织中NF-κB的激活起到减轻aGVHD的作用.
목적 탐토붕체좌미대소서급성이식물항숙주병(aGVHD)적억제작용급기가능궤제.방법 이C57BL/6소서위공서,획취골수세포급비세포.이Balb/c소서위수서,공분위5조:공백대조조(n=17)소서불여임하처리;단순조사조(n=17)소서부접수7.0 Gy X사선전신조사(TBI);약물대조조(n=17)소서야접수TBI,병차유미정맥주사붕체좌미;aGVHD조(n=8)소서TBI후주사공서골수세포급비세포;실험조(n=8)소서TBI후수주공서골수세포급비세포,병여이붕체좌미.관찰각조소서aGVHD적발생정황、존활시간급감합상태,단백인적법측정공백대조조、단순조사조화약물대조조소서간장급소장조직세포핵중핵인자κB(NF-κB)p65적표체.결과 aGVHD조화실험조적림상aGVHD평분분별위7.37±0.32화5.85±0.40,실험조명현저우aGVHD조(P＜0.05).aGVHD조수서간장、소장급피부조직위Thomas GVHD병리분급Ⅲ～Ⅳ급개변.실험조수서간장、소장급피부조직위Ⅰ～Ⅲ급GVHD개변,교aGVHD조유소감경.실험조존활시간장우aGVHD조(P＜0.05).aGVHD조화실험조소서이식후12 d시외주혈세포중H-2Kb분자양성세포적백분솔균＞90%.약물대조조간장급소장조직세포핵내NF-κB p65표체균고우단순조사조(P＜0.05).결론 붕체좌미가능통과재일정정도상억제조사예처리손상소치간장급소장조직중NF-κB적격활기도감경aGVHD적작용.
Objective To observe the effect of bortezomib on acute graft-versus-host disease (aGVHD) in an aGVHD model of mice and investigate the related mechanism. Methods Male C57BL/6( H-2Kb)mice were used as donors and female Balb/c (H-2Kd) mice used as recipients. Balb/c mice received total body irradiation (TBI) by 7.0 Gy X-radiation, and randomly divided into five groups. normal (group A), TBI (group B), TBI + bortezomib (group C), TBI + bone marrow cells (BMC) + spleen cells (SC) (group D) and TBI + bortezomib + BMC + SC (group E). The physical signs and the pathological damage of aGVHD, mean survival time, and chimerism were observed in recipients. The NF-κB p65 levels in nuclei of the liver and small intestine tissues of groups A,B and C were analyzed by Western blot. Results ( 1 ) The clinical aGVHD score in group D was (7.37±0. 32), significantly higher than in group E (5.85 ± 0.40) (P＜0. 05). Histopathology of the gut, liver and skin illuminated that the Ⅲ-Ⅳ degree GVHD occurred in group D. The occurrence of aGVHD in group E was later than in group D. The symptoms and the pathological damage of aGVHD in group E were milder than in group D. The average survival time in group E was significantly longer than that in group D (P＜0.05). The percentage of donor-derived cells in recipient mice was above 90% at day 12 after transplantation; (2) NF-κB p65 levels in nuclei of the liver and small intestine tissues in group B was significantly higher than in group C on the day 1,3 and 5 (P＜0. 05). Conclusion Bortezomib can inhibit the activation and expression of NF-κB,which may be the underlying mechanism for it to relieve aGVHD.