利多卡因通过抑制nf-理κb的活化减轻大鼠内毒素性肺损伤.docVIP

利多卡因通过抑制NF-κB的活化减轻大鼠内毒素性肺损伤 徐州医学院附属医院麻醉科，江苏 徐州 221002 封光 刘苏 王光磊 刘功俭* [摘要] 目的：探讨利多卡因对大鼠内毒素性肺损伤的保护作用及其机制。方法： SD大鼠随机分为1) control组 (0.9% sodium chloride); 2) LPS组; 3) LPS +lido1mg/kg组; 4) LPS +lido2mg/kg组; 5) LPS +lido4mg/kg组，其中LPS组和LPS +lido4mg/kg组又根据腹腔注射内毒素到取肺组织或收集血液标本的时间分为1、3、6、12h亚组。Western印迹检测大鼠肺组织核内NF-κB和胞浆IκBα的表达，ELISA检测血清TNF-α及IL-6的水平，观察大鼠肺组织病理变化。结果：大鼠腹腔注射内毒素后，肺组织核内NF-κB的表达明显增多，血清TNF-α及IL-6的水平明显升高，胞浆IκBα表达显著减少，病理切片示肺组织结构破坏严重。应用利多卡因后，与LPS组相比，核内NF-κB的表达明显减少，胞浆中IκBα表达显著增加，血清中TNF-α及IL-6的水平也明显降低，肺组织结构的破坏有明显减轻。结论：应用利多卡因能明显抑制内毒素引起的NF-κB的活化和TNF-α、IL-6的表达。提示利多卡因的肺保护作用机制可能与抑制NF-κB的活化，进而抑制炎症反应有关，而利多卡因对NF-κB活化的抑制可能与其抑制IκBα的降解有关。 Summary Background and Objectives: Lidocaine has been reported to attenuate the inflammatory response in addition to its anesthetic activity, but the mechanisms are poorly understood. The objective of this study is to determine if Lidocaine prior to endotoxemia diminishes pulmonary dysfunction by blocking the NF-kappa B activation. Methods: Rats were assigned to: 1) control (0.9% sodium chloride); 2) LPS; 3) LPS +lido1mg/kg; 4) LPS +lido2mg/kg; 5) LPS +lido4mg/kg. LPS and LPS+lido4mg/kg groups were subjected to 1h、3h、6h and 12h time point. To investigate the activation of NF-kappa B, the expression of NF-kappa B in the nuclear and I kappa B alpha in the cytosol were analyzed by western blot. The concentration of TNF-alpha and IL-6 in serum was detected by ELISA. The pathologic changes of lung were observed using HE staining. Results: After i.p. injection of LPS, the expression of NF-kappa B in the nuclear extracts was significantly increased and I kappa B alpha in the cytosol extracts was markedly decreased. The concentration of TNF-alpha and IL-6 in serum was increased. Pathological examination showed that the normal structure of lung was destroyed badly. However Lidocaine reversed above results. Conclusion: Lidocaine attenuates LPS-induced lung injury via mechanisms involving inhibiting NF-kappa B activation and cytokines release, which impli