摘要
目的探讨右美托咪定(Dex)对脓毒症肺损伤大鼠的保护作用及其机制。方法雄性SD大鼠100只,随机分为4组,每组25只。Ⅰ组为假手术组,Ⅱ、Ⅲ、Ⅳ组采用盲肠结扎穿孔法(CLP)建立脓毒症模型。Ⅱ组为模型对照组;Ⅲ组分别于CLP手术后0,2,4,6 h腹腔注射Dex 12.5μg·kg-1;Ⅳ组分别于CLP手术后0,2,4,6 h腹腔注射Dex25.0μg·kg-1。CLP手术后0,2,4,6,24 h分别测定肺组织肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6浓度,CLP后24 h酶联免疫吸附测定(ELISA)法测定肺组织高迁移率族蛋白B1(HMGB1)水平,Western blot测定肺组织Toll样受体4(TLR4)表达,检测肺组织湿/干质量比(W/D),苏木精-伊红染色观察肺组织的病理变化。结果与Ⅱ组比较,Ⅲ组和Ⅳ组中肺组织TNF-α、IL-6及HMGB1水平明显降低(P<0.05),肺组织TLR4表达及W/D明显降低,病理学损伤也明显减轻(P<0.05)。Ⅲ、Ⅳ组之间差异无统计学意义。结论 Dex抑制炎症反应从而减轻脓毒症大鼠的肺损伤,其机制可能通过抑制TLR4通路来实现。
Objective To investigate the protective effect of dexmedetomidine （Dex） on septic lung injury in rats. Methods One hundred male SD rats were randomly divided into four groups （n = 25 in each group）. Group Ⅰ was treated with sham operation only. Groups Ⅱ , Ⅲ, and IV received cecal ligation and puncture （CLP） to create the sepsis model. Group Ⅱ served as model control, group Ⅲ and Ⅳ received intraperitoneal injections of Dex at 12.5 and 25.0 μg·kg-1 , respectively, at 0,2,4 ,and 6 hours after CLP. TNF-α and IL-6 in lung tissue were measured at 0,2,4,6, and 24 h. ELISA was used to detect the levels of HMGB1, TNF-α and IL-6 at 24 h. The expression of TLR4 protein was assessed by western blotting. The acute lung injury was detected by HE stain and W/D ratio. Results In groups Ⅲ and Ⅳ, the expressions of TNF-oL and IL-6 were decreased significantly compared with group Ⅱ （ P〈0.05 ）. The expression of TLR4 in lung tissue and W/I） ratio were decreased in groups Ⅲ and Ⅳ compared with group Ⅱ （ P 〈 0.05 ）. There was no significant difference between group Ⅲ and Ⅳ. Conclusion - Dexmedetomidine can attenuate lung inflammatory reaction and lung injury in septic rats, the mechanism of which may be related to suppression of TLR4 pathway.
出处
《医药导报》
CAS
2015年第1期22-25,共4页
Herald of Medicine
关键词
右美托咪定
脓毒症
损伤
肺
炎症反应
Dexmedetomidine
Septic
Injury, lung
Inflammatory reaction
