CAJ | 학술논문

目的建立小鼠异基因骨髓移植后急性移植物抗宿主病(aGVHD)模型,探讨外源性白细胞介素7(IL-7)受体α(IL-7R α)干预小鼠aGVHD的疗效及可能机制.方法以BALB/C(H-2d)雌性小鼠为受鼠,将受鼠分为单纯照射组、照射移植组、IL-7Rα干预组3组,每组10只,均接受9 Gy 60Co进行全身照射,取C57BL/6(H-2b)供鼠骨髓细胞1×107个和脾细胞2×107个经尾静脉输注给受鼠,观察受鼠的体征、造血功能恢复及生存时间的变化,并进行病理学、嵌合体及细胞因子水平的检测.结果单纯照射组小鼠照射后逐渐死亡；照射移植组和IL-7Rα干预组小鼠移植后出现了典型的aGVHD症状,IL-7Rα干预组体征较照射移植组轻,生存时间较长,IL-7R α干预组外周血白细胞计数+14、+21、+28天造血功能恢复情况与照射移植组比较[(4.53±0.21)×109/L、(3.63±0.06)×109/L、(4.31±0.04) ×109/L与(1.81±0.05)×109/L、(1.32±0.04)×109/L、(1.76±0.04)×109/L],差异有统计学意义(t值分别为0.237、0.108、0.359,均P＜0.05)；肝、脾、皮肤组织的病理学结果显示,IL-7Rα干预组较照射移植组轻；嵌合体植入成功；移植后+7天血浆IL-7水平显著增高,随时间变化IL-7Rα干预组+14、+21天IL-7浓度与照射移植组比较[(194.32±1.02)、(131.63±1.54) pg/ml与(330.24±8.08)、(184.09±2.05)Pg/ml],差异有统计学意义(t值分别为1.590、1.285,均P＜0.05).结论建立了稳定的aGVHD小鼠模型；在aGVHD发生早期血浆IL-7水平显著增高；外源性IL-7R α可降低血浆IL-7水平,从而减轻异基因骨髓移植后aGVHD的发生.
목적 건립소서이기인골수이식후급성이식물항숙주병(aGVHD)모형,탐토외원성백세포개소7(IL-7)수체α(IL-7R α)간예소서aGVHD적료효급가능궤제.방법 이BALB/C(H-2d)자성소서위수서,장수서분위단순조사조、조사이식조、IL-7Rα간예조3조,매조10지,균접수9 Gy 60Co진행전신조사,취C57BL/6(H-2b)공서골수세포1×107개화비세포2×107개경미정맥수주급수서,관찰수서적체정、조혈공능회복급생존시간적변화,병진행병이학、감합체급세포인자수평적검측.결과 단순조사조소서조사후축점사망；조사이식조화IL-7Rα간예조소서이식후출현료전형적aGVHD증상,IL-7Rα간예조체정교조사이식조경,생존시간교장,IL-7R α간예조외주혈백세포계수+14、+21、+28천조혈공능회복정황여조사이식조비교[(4.53±0.21)×109/L、(3.63±0.06)×109/L、(4.31±0.04) ×109/L여(1.81±0.05)×109/L、(1.32±0.04)×109/L、(1.76±0.04)×109/L],차이유통계학의의(t치분별위0.237、0.108、0.359,균P＜0.05)；간、비、피부조직적병이학결과현시,IL-7Rα간예조교조사이식조경；감합체식입성공；이식후+7천혈장IL-7수평현저증고,수시간변화IL-7Rα간예조+14、+21천IL-7농도여조사이식조비교[(194.32±1.02)、(131.63±1.54) pg/ml여(330.24±8.08)、(184.09±2.05)Pg/ml],차이유통계학의의(t치분별위1.590、1.285,균P＜0.05).결론 건립료은정적aGVHD소서모형；재aGVHD발생조기혈장IL-7수평현저증고；외원성IL-7R α가강저혈장IL-7수평,종이감경이기인골수이식후aGVHD적발생.
Objective To establish a mouse model of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation,and using exogenous interleukin-7 receptor alpha (IL-7Rα) intervene mice aGVHD and analyse its possible mechanism.Methods The BALB/C (H-2d) female mice as recipients were grouped by rat: the irradiation group (group A),irradiation transplantation group (group B) and IL-7Rα in the intervention group (group C),each 10.ALL mice were accepted 9 Gy60Co total body irradiation.1×107 bone marrow cells and 2×107 spleen cells of donor C57BL/6 (H-2b) via the tail vein were infused to recipient mice.The signs of the recipient mice,hematopoietic functional recovery and survival time of change,and pathology,chimerism and cytokine levels in checkwere observed.Results Mice in A group after irradiation were gradually death,in group B and group C mice after transplantation had typical aGVHD symptoms,but lighter signs and a longer survival time of Group C than in group B.WBC count in Group C was +14 d (4.53± 0.21) ×109/L,+21 d (3.63±0.06) ×109/L,+28 d (4.31±0.04) ×109/L,was hematopoietic recovery compared with Group B [+14 d (1.81±0.05) ×109/L,+21 d (1.32±0.04) ×109/L,+28 d (1.76±0.04) ×109/L],the difference was statistically significant (t =0.237,0.108,0.359,P ＜ 0.05).The pathological results of liver,spleen,skin histopathology in group C were better than group B.Chimera implants,plasma IL-7 levels after transplant +7 d,concentration was significantly increased.IL-7 concentration in group C was +14 d (194.32±1.02) pg/ml,+21 d (131.63±1.54) pg/ml and in group B was +14 d (330.24±8.08) pg/ml,+21 d (184.09±2.05) pg/ml,the difference was statistically significant (t =1.590,1.285,P ＜0.05).Conclusion The stable aGVHD mouse model was established.In aGVHD early,plasma IL-7 levels were significantly increased.Exogenous IL-7Rαcan reduce the plasma IL-7 levels,thereby reducing the incidence of aGVHD after allogeneic bone marrow transplantation.