【目的】 探讨甲基莲心碱对脓毒症大鼠急性肺损伤的治疗作用及机制。【方法】 采用盲肠结扎穿刺（GLP）法制备脓毒症大 鼠模型，造模成功后，将大鼠分为模型组，甲基莲心碱低、高剂量组和甲基莲心碱高剂量+ PMA[核转录因子κB（NF-κB）激 活剂佛波酯]组，同时设置假手术组，每组15只。术后6 h，给予相应干预，连续2 d。采用苏木素-伊红（HE）染色观察肺组 织形态学改变，并进行损伤病理评分；检测肺组织湿干质量比；血气分析仪检测动脉血氧分压（PaO2）和动脉血二氧化碳分压 （PaCO2）水平；酶联免疫吸附法（ELISA）测定支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、 白细胞介素 6（IL-6）水平；Western Blot 法检测肺组织中 NF-κB p65、磷酸化 NF-κB（p-NF-κB）p65（Ser536）、环氧合酶 2 （COX-2）蛋白表达水平。【结果】 与假手术组比较，模型组大鼠肺组织损伤严重，肺组织损伤病理评分、湿干质量比及PaCO2 水平显著升高（P＜0.01），PaO2水平显著降低（P＜0.01），BALF 中 TNF-α、IL-1β、IL-6 水平以及肺组织中 p-NF-κB p65/ NF-κB p65比值、COX-2蛋白表达水平显著升高（P＜0.01）；与模型组比较，甲基莲心碱低、高剂量组大鼠肺组织损伤明显 改善，肺组织损伤病理评分、湿干质量比及 PaCO2水平显著降低（P＜0.05 或 P＜0.01），PaO2水平显著升高（P＜0.05 或 P＜ 0.01），BALF中TNF-α、IL-1β、IL-6水平以及肺组织中p-NF-κB p65/NF-κB p65比值、COX-2蛋白表达水平显著降低（P＜ 0.05或P＜0.01）。然而，PMA干预后，甲基莲心碱对脓毒症大鼠肺组织损伤的改善作用被明显逆转（P＜0.01）。【结论】 甲基 莲心碱可改善大鼠脓毒症急性肺损伤及肺功能，其作用可能与抑制NF-κB信号通路激活，进而减少体内炎症因子释放有关。

Objective To investigate the therapeutic effect of Neferine on acute lung injury in sepsis rats and its mechanism. Methods A rat sepsis model was prepared by cecal ligation and puncture（CLP） method. After successful modeling， the rats were divided into model group， neferine low- and high- dose groups， neferine high-dose+PMA [nuclear factor kappa B（NF-κB）activator phorbol ester] group，and sham operation group was set up，with 15 rats in each group. At 6 hours after operation，the corresponding intervention was given for 2 days. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of lung tissue， and the pathological damage score was performed. The wet-dry mass ratio of lung tissue was detected；the levels of arterial partial pressure of oxygen（PaCO2）and arterial partial pressure of carbon dioxide（PaCO2）were detected by blood gas analyzer. The levels of tumor necrosis factor α（TNF-α），interleukin 1β（IL-1β）and interleukin 6（IL-6）in bronchoalveolar lavage fluid（BALF）were measured by enzyme-linked immunosorbent assay（ELISA）. The protein expression levels of NF- κB p65， phosphorylated NF- κB（p-NF- κB）p65（Ser536）and cyclooxygenase-2 （COX-2）in lung tissue were detected by Western Blot. Results Compared with the sham operation group，the pathological injury of lung tissue in the model group was severe，the pathological injury score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly increased（P＜0.01），PaO2 level was significantly decreased（P＜0.01），the levels of TNF-α，IL-1β and IL-6 in BALF，the ratio of p-NF-κB p65/NF-κB p65 and the protein expression level of COX-2 in lung tissue were significantly increased（P＜0.01）. Compared with the model group， the pathological damage of lung tissue in the low-dose and high-dose neferine groups was significantly improved，the pathological damage score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly decreased（P＜0.05 or P＜0.01），PaO2 level was significantly increased（P＜0.05 or P＜0.01）， the levels of TNF- α， IL-1β and IL-6 in BALF， the ratio of p-NF- κB p65/NF- κB p65 and the protein expression level of COX-2 in lung tissue were significantly decreased（P＜0.05 or P＜0.01）. However，after PMA intervention，the improvement of neferine on lung tissue injury in septic rats was significantly reversed（P＜0.01）. Conclusion Neferine can improve acute lung injury and lung function in rats with sepsis，which may be related to inhibiting the activation of NF- κB signaling pathway and thereby reducing the release of inflammatory factors in vivo.

R285.5

江西省卫生健康委科技计划项目（编号：SKJP220211237）