桑黄素在脂多糖诱导的急性肺损伤中的相关机制

doi:10.3969/j.issn.1004-616x.2022.03.008

摘要/Abstract

摘要： 目的： 探究桑黄素在脂多糖(LPS)诱导的急性肺损伤(ALI)中的相关机制。方法： 将32只雄性C57BL/6小鼠随机分为对照组(生理盐水)、ALI模型组(LPS处理)、LPS+桑黄素低浓度(25 mg/kg)处理组和LPS+桑黄素高浓度(50 mg/kg)处理组，共4组，每组8只。LPS(6 mg/kg)溶液经气管滴入小鼠气道刺激支气管及肺组织建立ALI模型。桑黄素溶液经腹腔注射给药3 d后，收取双肺，对一部分肺组织测定湿/干质量比，进行HE染色和组织病理学观察。采用实时荧光定量PCR(qPCR)和Western blot检测肺组织中氧化应激信号通路相关基因(NOX1、NOX4、Nrf2和HO-1)的表达情况。结果： HE染色和肺湿/干质量比测定结果显示气道滴入LPS成功构建了ALI小鼠模型，与对照组比较，桑黄素处理可有效缓解LPS诱导的急性肺损伤。qPCR和Western blot实验结果显示，与对照组比较，ALI模型组肺组织中，Nrf2和HO-1的表达上调(P<0.01)；与ALI模型组比较，桑黄素处理可显著降低肺组织NOX1和NOX4的表达(P<0.05或P<0.01)；且桑黄素处理可进一步上调Nrf2和HO-1的表达从而抑制氧化应激的发生(P<0.05或P<0.01)。结论： 氧化应激的发生参与ALI 的发生发展，桑黄素可通过激活Nrf2-HO-1信号通路降低NOX1和NOX4表达抑制氧化应激，从而减缓LPS引起的肺损伤。

关键词: 桑黄素, 脂多糖, 急性肺损伤, 氧化应激

Abstract: OBJECTIVE： To investigate mechanisms of morin in lipopolysaccharide (LPS)-induced acute lung injuries (ALI). METHODS： The ALI model was established by in vivo experiments in male C57BL/6 mice which were divided into four groups：control (saline)，LPS-treated ALI，LPS+morin (25 mg/kg)，and LPS+morin (50 mg/kg) groups. LPS (6 mg/kg) solution was instilled into the airways of mice through the trachea to stimulate bronchial and lung tissues after 3 days of intraperitoneal injection of morin solution at a concentration of 25 mg/kg or 50 mg/kg. Both lungs were harvested from each mouse. Some lung tissues were stained with HE and the others for measurements of ratio of lung wet mass to dry mass，and histopathological observations were conducted. Real-time quantitative PCR (qPCR) and Western blot were used to detect expressions of oxidative stress signaling pathway-related genes (NOX1，NOX4，Nrf2 and HO-1) in lung tissues. RESULTS： Compared with the control group，HE staining and the ratio of lung wet mass to dry mass showed that airway instillation of LPS successfully established a mouse model of acute lung injury，and morin can effectively alleviate the LPS-induced injury. The results of qPCR and Western blot experiments showed that expressions of Nrf2 and HO-1 were up-regulated in the lung tissue of the LPS-stimulated ALI model group (P<00.01)，compared with the control group. Morin treatment significantly reduced the expressions of NOX1 and NOX4 (P<00.05 or P<00.01). Furthermore， and morin treatment up-regulated expressions of Nrf2 and HO-1 to inhibit the occurrence of oxidative stress (P<00.05 or P<00.01)，compared with the ALI model group. CONCLUSION： Oxidative stress was involved with the occurrence and development of ALI. In addition，the Nrf2-HO-1 signaling pathway reduced the expression of NOX1 and NOX4 through the activation of morin，and inhibit oxidative stress，thereby slowing the alveolar edema and lung tissue fibrosis caused by LPS.

Key words: morin, lipopolysaccharide, acute lung injury, oxidative stress

中图分类号:

R285.5

于婧, 冯丹丹, 潘文森. 桑黄素在脂多糖诱导的急性肺损伤中的相关机制[J]. 癌变·畸变·突变, 2022, 34(3): 213-218.

YU Jing, FENG Dandan, PAN Wensen. The related mechanism of morin in lipopolysaccharide induced acute lung injury[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(3): 213-218.

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