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“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

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

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【作者】 袁兆新刘潇季东平张旭王志李扬赵雪俭孙连坤

【Author】 YUAN Zhao-xin~ 1,2 , LIU Xiao~1, JI Dong-ping~ 1,2 , ZHANG Xu~2, WANG Zhi~1, LI Yang~1, ZHAO Xue-jian~1, SUN Lian-kun~1 (~1Department of Pathophysiology, Basic Medical College, Jilin University, Changchun 130021, China;~2Changchun Medical College, Changchun 130031, China)

【机构】 吉林大学基础医学院病理生理教研室长春医学高等专科学校吉林大学基础医学院病理生理教研室 吉林长春130021吉林长春130031吉林长春130021

【摘要】 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MAP40mmHg,维持10min(失血性休克),然后舌下静脉注射LPS(1·5mg/kg)。4h后留取肺脏组织,RT-PCR法测定IκBα和TLR4mRNA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TLR4mRNA表达明显低于HS+LPS组(P<0·05);HS+LPS+SM组IκBαmRNA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TLR4mRNA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。

【Abstract】 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.

【基金】 吉林大学创新基金资助项目(No.2003CX100)
  • 【文献出处】 中国病理生理杂志 ,Chinese Journal of Pathophysiology , 编辑部邮箱 ,2006年04期
  • 【分类号】R363
  • 【被引频次】23
  • 【下载频次】135
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