实用医学杂志 ›› 2022, Vol. 38 ›› Issue (15): 1896-1900.doi: 10.3969/j.issn.1006⁃5725.2022.15.009

• 基础研究 • 上一篇    下一篇

青藤碱调控Nrf2/Keap1信号通路对脓毒症急性肺损伤的改善作用 

王慧 龚园其 周仪华 蓝海兵 张啸    

  1. 南昌大学第二附属医院重症医学科（南昌330000）

  • 出版日期:2022-08-10 发布日期:2022-08-10
  • 基金资助:
    国家自然科学基金项目（编号：81860349）

Alkaloid sinomenine improves acute lung injury in sepsis by activating Nrf2/Keap1 signaling pathway

WANG Hui，GONG Yuanqi，ZHOU Yihua，LAN Haibing，ZHANG Xiao.   

  1. Department of Critical Care Medicine，the Second Affiliated Hospital of Nanchang University，Nanchang 330000，China

  • Online:2022-08-10 Published:2022-08-10

摘要：

目的 基于 Nrf2/ Keap1 信号通路探究青藤碱（Alkaloid sinomenine，SIN）对脓毒症急性肺损 伤的影响。方法 采用盲肠结扎穿孔术诱导建立脓毒症大鼠模型。将 60 只 SD 大鼠随机分成 ALI 组、假 手术组、SIN 组（40⁃SIN 组、80⁃SIN 组、160⁃SIN 组），每组 12 只。采用评分法评价各组大鼠脓毒症严重程 度；HE 染色观察大鼠肺组织病理变化；比色法检测大鼠肺组织氧化应激因子超氧化物歧化酶（superoxide dismutase，SOD）和丙二醛（malondialdehyde，MDA）活性；ELISA 法检测肺组织中肿瘤坏死因子⁃α（tumor necrosis factor⁃α，TNF⁃α）、白介素（interleukin⁃1β，IL⁃1β）和（interleukin⁃6，IL⁃6）水平；Western blot 和 qRT⁃ PCR 分别检测肺组织中 Nrf2、Keap1、HO⁃1 蛋白和 mRNA 的表达水平。结果 与 ALI 组对比，40⁃SIN、80⁃ SIN、160⁃SIN 组脓毒症急性肺损伤的肺组织评分减小（P < 0.01）；40⁃SIN、80⁃SIN、160⁃SIN 组肺组织氧化指 标 SOD 活性增强，MDA、IL⁃1β、TNF⁃α、IL⁃6 水平降低（P < 0.01）；40⁃SIN、80⁃SIN、160⁃SIN 组大鼠亦有少量巨噬细胞，肺间质稍有水肿，肺组织病理损伤得到了一定的缓解，且呈量⁃效关系，且高剂量组大鼠肺组织 改善病变程度效果最佳。与 ALI 组对比，40⁃SIN、80⁃SIN、160⁃SIN 组肺组织中 Nrf2、HO⁃1 蛋白及 mRNA 表达 量明显升高（P < 0.01），大鼠肺组织中 Keap1 蛋白及 mRNA 表达量明显降低（P < 0.01）。结论 SIN 可增强 SOD 活性，降低 MDA、IL⁃1β、TNF⁃α、IL⁃6 水平，调节 Nrf2/Keap1 信号通路，进而缓解肺组织损伤程度，保护肺组织，改善脓毒症引起的急性肺损伤。

关键词:

青藤碱, Nrf2/Keap1信号通路, 脓毒症, 急性肺损伤

Abstract:

Objective To explore the effect of Alkaloid sinomenine（SIN）on acute lung injury in sepsis through Nrf2/Keap1 signaling pathway. Methods A rat model of sepsis was established by cecal ligation and puncture. Sixty SD rats were randomly divided into ALI group，sham operation group and SIN group（40⁃SIN group， 80⁃SIN group，160⁃SIN group），with 12 rats in each group. The severity of sepsis in each group was evaluated by scoring method；HE staining was used to observe the pathological changes of rat lung tissue，SOD and aldehyde （malondialdehyde，MDA）activity；ELISA method to detect tumor necrosis factor⁃α（TNF⁃α），interleukin（inter⁃ leukin⁃1β，IL⁃1β）and（interleukin⁃6，IL⁃6）in lung tissue ）levels. Western blot and qRT⁃PCR were used to detect the expression level of Nrf2，Keap1，HO⁃1 protein and mRNA in lung tissue，respectively. Results Compared with ALI group，40⁃SIN，80⁃SIN，and 160⁃SIN group had lower lung tissue scores in acute lung injury in sepsis （P < 0.01）. The activity of SOD was enhanced，and the level of MDA，IL⁃1β，TNF⁃α，and IL⁃6 was decreased （P < 0.01）. The interstitial edema was slight；pathological damage of the lung tissue was relieved to a certain extent. There was a dose⁃effect relationship，and the high⁃dose group had the best effect on improving the lesion degree of the lung tissue. Compared with those in ALI group，the protein and mRNA expressions of Nrf2 and HO⁃1 in the lung tissue of the 40⁃SIN，80⁃SIN and 160⁃SIN group were significantly up⁃regulated（P < 0.01），and the protein and mRNA expressions of Keap1 in the lung tissue of the rats were significantly down⁃regulated（P < 0.01）. Conclusion SIN can enhance the activity of SOD，reduce the level of MDA，IL⁃1β，TNF⁃α，IL⁃6，and regulate Nrf2/Keap1 signaling pathway，thereby alleviating the degree of lung tissue damage，protecting lung tissue，and improving acute lung disease caused by sepsis.

Key words: Alkaloid sinomenine,  , Nrf2/Keap1 signaling pathway,  , sepsis,  , acute lung injury

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