“失血加LPS”大鼠肺脏IκBα和TLR4基因表达及参麦的肺脏保护作用

目的： 探讨参麦注射液的抗休克效果及其作用机制。 方法： 大鼠随机分为单纯失血性休克（HS）组、失血加脂多糖（HS+LPS）组、地塞米松（HS+LPS+Dex）组和参麦注射液（HS+LPS+SM）组。HS+LPS组大鼠模型复制：首先，大鼠放血至MAP 40 mmHg,维持10 min（失血性休克），然后舌下静脉注射LPS（1.5 mg/kg）。4h后留取肺脏组织,RT-PCR法测定IκBα和TLR4 mRNA表达、ELISA法测TNF-α含量，并进行肺脏组织电镜观察。 结果： HS+LPS+SM组TLR4 mRNA表达明显低于HS+LPS组（P<0.05）；HS+LPS+SM组IκBα mRNA表达明显高于HS+LPS组（P<0.05）；HS+LPS+SM组肺脏组织匀浆TNF-α含量明显低于HS+LPS组（P<0.05）；HS+LPS+SM组肺组织病理损伤显著轻于HS+LPS组。 结论： 参麦注射液能够下调肺脏组织中TLR4 mRNA表达，同时上调IκBα的表达，进而抑制促炎介质TNF-α释放，提示参麦注射液可能通过调节NF-κB信号转导途径抑制炎症反应而对机体细胞起保护作用。

Effects of Shenmai injection on IκB and TLR4 mRNA expression in lungs of rats exposed to hemorrhagic and LPS shock

AIM: To explore the molecular mechanism of anti-shock effect of Shenmai (SM) injection and to observe its influence on TLR4 and IκB mRNA expression in hemorrhagic shock (HS) plus LPS rat lung. METHODS: Rats were divided into HS, HS+LPS, HS+LPS+ dexamethasone (DEX), HS+LPS+SM group, respectively. HS+LPS injury model of rats were induced by hemorrhagic shock (MAP 40 mmHg for 10 min) followed by intravenous administration of lipopolysaccharide (LPS, 1.5 mg/kg). Four hours later, the TNF-α contents in lung tissue were measured by ELISA, TLR4 mRNA and IκBα mRNA expression were assayed by RT-PCR, ultrastructural changes of the type Ⅱ alveolar cell were observed by electron microscope. RESULTS: The TLR4 mRNA expression level in HS+LPS+SM group was significantly decreased as compared to HS+LPS group (P<0.05). Otherwise, the level of IκBα mRNA expression in HS+LPS+SM group was significantly increased as compared to HS+LPS group (P<0.05). The TNF-α content in lung tissue in HS+LPS+SM group was obviously lower than that in HS+LPS group (P<0.05). In HS+LPS+SM group, the lung pathological injuries were alleviated as compared to HS+LPS group. CONCLUSION: Shenmai injection down-regulates TLR4 mRNA expression and up-regulates IκBα mRNA expression in the lung, and inhibits the release of TNF-α in rats exposed to HS and LPS. These results suggest that Shenmai injection might have a protective effect on the tissue injured from hemorrhagic shock and endotoxic shock by regulating NF-κB signal transduction pathway and inhibiting pro-inflammatory cytokine production.