多器官功能障碍综合征小鼠脾脏高迁移率族蛋白B1及免疫细胞功能变化的研究  

Effect of change in high mobility group protein box 1 expression on activity of immunocytes in spleen of mice with multiple organ dysfunction syndrome

作　　者：吕艺[1] 陆江阳[2] 赵敏[2] 李志宏[2] 杨毅[2] 

机构地区：[1]解放军总医院第一附属医院创伤外科研究室,北京100037 [2]解放军总医院第一附属医院病理科,北京100037

出　　处：《中国危重病急救医学》2009年第1期25-28,65,共5页Chinese Critical Care Medicine

基　　金：全军医学科研“十一五”计划项目（06MB307）;首都医学发展科研基金项目（2003-3025）

摘　　要：目的观察多器官功能障碍综合征（MODS）小鼠脾脏高迁移率族蛋白B1（HMGB1）与主要组织相容复合体（MHC）-Ⅱ类分子I-A^b表达变化的规律，探讨HMGB1对脾脏免疫细胞功能状态的影响及其与MODS病程发展的关系。方法选择57BL／6小鼠90只，按随机数字表法分为正常对照组，致伤后3、8、12h及1、2、3、5和10～12d组，每组10只。采用腹腔注射酵母多糖的方法复制小鼠MODS模型；检测小鼠脾脏HMGB1和I—A^b表达水平及脾脏免疫细胞的凋亡率。结果正常小鼠脾脏中仅有少量HMGB1mRNA表达；在MODS病程中呈双峰升高，表现为伤后1～2dHMGB1mRNA表达量达高峰（P〈0．01），随后表达下调，伤后5d明显减少，但在10～12d时表达再次升高（P〈0．05）；HMGB1蛋白表达量的变化与mRNA表达变化规律基本一致。在伤后8h脾脏单核细胞I—A^b与HMGBl蛋白表达同时升高（P〈0．01），随后两者在病程中呈反相变化。脾脏免疫细胞凋亡率在伤后呈双峰升高，与HMGB1变化规律一致。结论MODS小鼠脾脏HMGB1表达上调与淋巴细胞凋亡密切相关，并影响脾脏抗原呈递细胞对MHC-Ⅱ类分子的表达，由此削弱细胞免疫应答能力，影响MODS的病情发展。Objective To explore the regularity of high mobility group protein box 1 （HMGB1） expression and major histocompability complex Ⅰ I-A^b in spleen of mice with multiple organ dysfunction syndrome （MODS）, and its effect on the activity of immunocytes and relationship with pathogenesis of MODS. Methods MODS model was replicated by injecting zymosan into abdominal cavity of mice. The mice were randomly divided into normal control group, and 3, 8, 12 hours, and 1, 2, 3, 5, 10 - 12 days after injection groups. The expression levels of HMGB1, I-A^b and apoptosis rate in the spleen were detected. Results There was a little HMGB1 expression in the spleen of control mice. After zymosan administration, HMGB1 expression was increased, it reached the highest level on 1 2 days （P〈0.01）, decreased on day 5, then elevated on 10 - 12 days （P〈0.05）. Change in HMGB1 mRNA expression was in accordance with that of the protein. At 8 hours following injury, the I-A^b expressed on the splenocytes was enhanced similar to that of HMGB1, and then it reversed. The occurrence of splenocyte apoptosis was also consistent with change in HMGB1 content in the spleen. Conclusion The increased apoptosis of splenocytes in mice with MODS is closely related with up-regulation of HMGB1 expression, which inhibits the expression level of I-A^b on antigen presenting cells, thus weakens the capability of immune responses and affected the development of MODS.

关 键 词：多器官功能障碍综合征 脾脏 高迁移率族蛋白B1 主要组织相容复合体-Ⅱ类分子 细胞凋亡 

分 类 号：R686[医药卫生—骨科学]