Th1/Th2平衡在多器官功能障碍综合征发病过程中的变化
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军队“十五”医学研究重点课题(01L006).


Changes of Th1/Th2 balance in multiple organ dysfunction syndrome
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Supported by Key Medical Program of the 10th Five-year Plan of PLA(01L006).

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    摘要:

    目的:从Th1/Th2平衡角度出发探讨多器官功能障碍综合征(MODS)的发病机制。方法:将体质量22~30 kg健康雄性家猪随机分为MODS组和正常对照组,每组各9只。采用失血性休克复苏+内毒素血症复合因素建立猪MODS模型。MODS组于放血前,内毒素注射前,内毒素注射后1、24、48及72 h留取血标本,动物死亡后留取脾脏标本。正常对照组同时间点留取标本。ELISA法检测血清IFN-γ和IL-4含量变化;实时荧光PCR法测定脾脏IFN-γ、IL-4 mRNA水平及Th1/Th2细胞特异性转录因子T-bet和GATA-3 mRNA的含量变化。结果:内毒素注射后1 h血清IFN-γ和IL-4浓度达到峰值,后IFN-γ浓度下降较快,内毒素注射后72 h IFN-γ/IL-4比值显著低于基础值水平(P=0.000);MODS组脾脏IFN-γ/IL-4 mRNA比值降低明显,与对照组比较差异具有显著性(P=0.020);脾脏T-bet/GATA-3比值也显著低于对照组(P=0.038)。结论:MODS发生过程中存在Th1向Th2漂移现象。

    Abstract:

    Objective:To explore the pathogenesis of multiple organ dysfunction syndrome (MODS) with respect to the balance of Th1/Th2. Methods: Eighteen healthy male minipigs, weighing 22-30 kg, were randomly divided into two groups: MODS group and control group. Double-hit method including hemorrhagic shock and endotoxiemia was used to establish the porcine MODS model.The peripheral vein blood samples were collected at different time-points (before bloodletting, before endotoxin injection, 1 h, 24 h,48 h and 72 h after endotoxin injection) in the two groups. The spleen samples were collected after death of the animals. Plasma levels of IFN-γ and IL-4 were detected by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to detect the expression of IFN-γ, IL-4, T-bet and GATA-3 mRNA (The latter 2 were the key transcription factors associated with Th1/Th2 response) in the spleen samples.Results: The plasma levels of IFN-γ and IL-4 quickly reached the peak values 1 h after the endotoxin injection, then the level of IFN-γ decreased quickly. The ratio of IFN-γ/IL-4 was significantly lower than the baseline value 72 h after endotoxin injection(P=0.000). The ratio of IFN-γ/IL-4 mRNA in MODS group was obviously lower than that in the control group(P=0.020); the ratio of T-bet/GATA-3 was also lower in MODS group(P=0.038).Conclusion: The shift from Th1 to Th2 occurs in the progress of MODS.

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历史
  • 收稿日期:2007-01-24
  • 最后修改日期:
  • 录用日期:2007-12-17
  • 在线发布日期: 2007-12-17
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