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Flt3配体体内扩增肺树突细胞对多器官功能障碍综合征模型小鼠的免疫治疗作用观察
  • ISSN号:0577-7402
  • 期刊名称:解放军医学杂志
  • 时间:2012
  • 页码:774-778
  • 分类:R365[医药卫生—病理学;医药卫生—基础医学]
  • 作者机构:[1]解放军总医院第一附属医院病理科,北京100048, [2]军事医学科学院微生物流行病研究所,北京100091
  • 相关基金:国家自然科学基金(81000848);全军医学科研“十一五”规划面上项目(06MB307)
  • 相关项目:转录因子Runx3诱导脓毒症树突状细胞分化成熟障碍的分子机制
中文摘要:

目的探讨fins样酪氨酸激酶3配体(Flt3L)体内扩增肺间质树突细胞(DCs)对多器官功能障碍综合征(MODS)的免疫治疗作用。方法雄性BALB/c小鼠80只,随机均分为正常对照组、Flt3L对照组、MODS模型组和Flt3L治疗组。腹腔注射酵母多糖复制MODS模型,Flt3L治疗于MODS模型复制后24h开始连续9d每天皮下注射(10μg/次)。观察各组动物病死率。12d后处死动物,取肺组织,用密度梯度离心法分离肺单个核细胞,流式细胞术检测DCs亚群数量百分比;全自动生化分析仪检测外周血丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、肌酐、血糖、脂肪酶和淀粉酶水平;光镜观察肺组织病理学变化。结果正常对照组和Flt3L对照组无死亡发生;Flt3L治疗组病死率明显低于MODS模型组(P〈0.05)。Flt3L对照组肺髓系CDllc^+CDllb^+、类浆系CDllc^+CD45R/B220^+和CDllc^+I-Ad^+DCs亚群比例明显高于正常对照组及MODS模型组(P〈0.0S),且正常对照组明显高于MODS模型组(P〈0.05),而Flt3L治疗组三个DCs亚群比例较MODS模型组显著上升(P〈0.05)。与正常对照组和Flt3L对照组比较,MODS模型组血清ALT、AST、脂肪酶、淀粉酶和肌酐水平明显升高,血糖水平明显下降(P〈0.OS),而与MODS模型组比较,Flt3L治疗组血清ALT、AST和肌酐水平明显下降,血糖水平明显上升(P〈0.05),肺组织损伤明显减轻。结论Flt3L可通过刺激肺DCs从而明显减轻MODS模型肺组织损伤,改善脏器功能,降低实验动物的病死率,具有潜在的免疫调节治疗作用。

英文摘要:

Objective To explore the therapeutic effect of Flt3 ligand (Flt3L) on multiple organ dysfunction syndrome (MODS) model via amplification of lung dendritic cells. Methods Animal model of MODS was replicated by injecting zymosan into the peritoneal cavity of BALB/c mice, and then the mice were randomly divided into Flt3L treatment group, MODS group, Flt3L group and control group. Mortality rate was observed. After 12 days, lung mononuclear cells were isolated by density gradient centrifugation and analyzed with flow cytometry. Blood AST, ALT, creatinine, lipase, amylase and glucose were determined by automatic biochemical analyzer. Pathological changes in lung tissue were observed under light microscope. Results Mortality in Flt3L treatment group decreased dramatically compared with MODS group. The proportions of myeloid, plasmacytoid and I-Ad^+ D Cs in Flt3L group were remarkably increased compared with control group, and the proportion of the three DC subsets in MODS group was much lower than that in control group. Howerver, Flt3L treatment dramatically increased the proportion of them in MODS group. In MODS group, the level of ALT, AST, lipase, amylase and creatinine remarkably increased and blood glucose decreased compared with that of Flt3L and control groups; but in Flt3L treatment group, the level of ALT, AST, lipase, amylase and creatinine decreased and blood glucose increased dramatically, and lung injury mitigated obviously compared with MODS group. Conclusion Flt3L could attenuate lung tissue injury in MODS model, improve organ function, and lower the mortality of experimental animals, thus exerting its immunotherapeutic effects by in vivo amplification of lung dendritic cells.

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期刊信息
  • 《解放军医学杂志》
  • 中国科技核心期刊
  • 主管单位:中国人民解放军总后勤部卫生部
  • 主办单位:人民军医出版社
  • 主编:
  • 地址:北京市100036信箱188分箱
  • 邮编:100036
  • 邮箱:mjcpla@pmmp.com.cn
  • 电话:010-51927306
  • 国际标准刊号:ISSN:0577-7402
  • 国内统一刊号:ISSN:11-1056/R
  • 邮发代号:2-74
  • 获奖情况:
  • 全军医学期刊质量评比优秀期刊奖,北京市全优期刊奖,中国科学引文数据库来源期刊
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),瑞典开放获取期刊指南,中国北大核心期刊(2000版)
  • 被引量:30614