摘要
目的探讨p38丝裂原激活的蛋白激酶（p38MAPK）抑制剂SB203580对小鼠异基因骨髓造血干细胞移植后急性移植物抗宿主病（aGVHD）的发生及小肠损伤的影响。方法用60只BALB／c小鼠作为受鼠，分为正常对照组、单纯照射组、模型组和干预组，每组15只。单纯照射组、模型组和干预组小鼠均接受7．5Gyy射线全身照射。C57BL／6小鼠作为供鼠，取其骨髓细胞及脾细胞经尾静脉输注给接受照射后的受鼠，建立小鼠aGVHD模型。干预组为aGVHD模型小鼠给予SB203580干预，末次给药48h后处死。模型组小鼠为aGVHD模型仅给予等量二甲基亚砜。移植后观察小鼠的一般状态和生存情况。移植后10d取各组小鼠小肠组织，采用RT-PCR、Westernblot及免疫组化方法检测磷酸化p38MAPK、Fas、FasL的表达。结果干预组小鼠的体重下降程度为（13．00±0．50）％，轻于模型组的（25．00±0．75）％，差异有统计学意义（P〈0．05）；干预组小鼠的aGVHD的临床评分（3．33±0．82）低于模型组（6．33±1．36），差异有统计学意义（P〈0．05）；干预组小鼠的小肠组织中磷酸化p38MAPK、Fas、FasL的相对表达水平分别为1．43±0．02、0．81±0．03、0．97±0．03，均显著低于模型组的1．76±0．05、1．52±0．04、1．48±0．04。结论SB203580可抑制aGVHD小鼠小肠组织中p38MAPK通路的活化，减少Fas和FasL信号通路所引起的细胞凋亡，有效减轻aGVHD的发生及靶器官小肠的损害。
Objective To explore the effects of p38MAPK inhibitor SB203580 （SB） on the occurrence of acute GVHD and intestine damage after allogeneic hematopoietie stem cell transplantation （allo-HSCT） in mice. Methods Sixty BALB/c mice, as recipients, were randomized to control group, irradiation group, model group and intervention group. C57BL/6 mice, as donors, were raised to prepare the bone marrow cells （BMCs） and spleen cells （SCs）, which were injected into irradiated recipients mice by tail vein. Except control group, other groups accepted 7.5Gy total body irradiation. Model group and intervention group were infused with BMCs 5×10^6 and SCs 5×10^5 by less than 4 h after irradiation. SB was injected into intervention group by intraperitoneally, but only DMSO for model group. The general status and survival rate of each group were evaluated. The expression of p-p38MAPK, Fas and FasL in intestine were determined by RT-PCR, Western blot and immunohistochemistry （IHC）. Results The weight changes of intervention group （13.00±0.50）% was significantly lighter than that of model group （25.00± 0.75）% （P〈0.05）. The clinical score of acute GVHD in the intervention group （3.33±0.82） was significantly lower than that of model group （6.33±1.36） （P〈0.05）. The expression levels of p-p38MAPK, Fas and FasL in small intestine of intervention group （1.43±0.02, 0.81±0.03, 0.97±0.03） were lower than those of model group （1.76±0.05, 1.52±0.04, 1.48±0.04）. Conclusion SB inhibited the activation ofp38MAPK and Fas/ FasL signal pathway and alleviated the apoptosis of small intestine. And SB could relieve small intestine damages induced by allogeneic T lymphocytes.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2013年第8期673-678,共6页
Chinese Journal of Hematology
基金
国家自然科学基金（81171590）
江苏省青蓝工程人才计划
