失血性大鼠休克后肠、肝、肺组织中细胞因子表达、释放时相及其伴随的病理变化

Expression and release-phases of pro-inflammatory cytokines in the intestine,liver,and lung in hemorrhagic shock rats

目的：探讨休克后促炎细胞因子的表达、释放时相及伴随的肠、肝、肺组织病理变化。方法：80只SD大鼠随机均分为失血性休克组和对照组。采用RT-PCR、ELISA方法检测失血性休克后30、60、90 min及复苏后30、90 min肠、肝、肺组织内TNF-α、IL-6 mRNA表达及血清中TNF-α、IL-6含量；HE和IHC染色检测伴随的组织病理变化。结果：①休克30 min时,肠、肝、肺内的促炎细胞因子表达未见升高；60 min时肠道先出现TNF-αmRNA表达升高(P<0．05)；而肝脏在90 min开始表达升高(P<0．05),肺脏则在复苏后30 min开始表达升高(P<0．05)。复苏后90 min肠、肝、肺的细胞因子表达都继续显著升高(P<0．01)。②TNF-αxmRNA在肠、肝、肺的表达升高最早,其后为IL-6mRNA。③30min时门静脉和外周血中TNF-α、IL-6的含量与对照组相比无显著差异,而60 min时门静脉血中含量显著升高(P<0．01)。④休克后肠黏膜坏死脱落；肝组织结构紊乱、肝窦增宽、肝细胞变性坏死；肺脏间质水肿、炎症细胞浸润。结论：失血性休克时细胞因子的释放顺序是肠道、肝脏和肺脏,推测存在”肠-肝-肺”细胞因子释放轴的可能,有待进一步确定。

Objective To investigate the kinetic features of expression and release of pro-inflammatory cytokines in vital organs in hemorrhagic shock rats, and the accompanying pathologic changes. Methods Eighty Sprague-Dawley rats were divided into hemorrhagic shock and control groups. RT-PCR was used to assess the expression of TNF-α and IL-6 mRNA in the intestinal, hepatic and pulmonary tissues. Simultaneously, ELISA was used to assess the level of TNF-α and IL-6 in the blood. Results （1）The level of pro-inflammatory cytokines was not increased at 30 minutes after shock. The intestine was the first organ to demonstrate TNF-α mRNA up-regulation（60 minutes after shock, P〈0.05）, followed by the liver（90 minutes after shock, P〈0.05） and the lung （30 minute after resuscitation, P〈0.05）. （2）The expression of TNF-α and IL-6 mRNA in the vital organs was successively increased after hemorrhagic shock and resuscitation, with the TNF-α first to appear. （3）The levels of TNF-α and IL-6 in the portal vein blood were elevated prior to ＂those in the peripheral blood. Conclusions There might exist a gut-liver-lung axis in the kinetics of expression and release of major pro-inflammatory cytokines after hemorrhagic shock.