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黄芪百合颗粒通过抑制氧化应激和TLR4/NF-κB/NLRP3炎症通路减轻低压低氧诱导的大鼠急性肺损伤。

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway.

作者信息

Zeng Yuanding, Cao Wangjie, Huang Yong, Zhang Han, Li Congyi, He Jianzheng, Liu Yongqi, Gong Hongxia, Su Yun

机构信息

Gansu University Key Laboratory for Molecular Medicine & Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China; Key Laboratory of Dunhuang Medicine, Ministry of Education, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu Province, China.

出版信息

J Ethnopharmacol. 2024 Apr 24;324:117765. doi: 10.1016/j.jep.2024.117765. Epub 2024 Jan 14.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Huangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe "Huangqi Baihe porridge" and the Dunhuang medical prescription "Cistanche Cistanche Soup." The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments.

AIM OF THE STUDY

The purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules.

MATERIALS AND METHODS

The HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR.

RESULTS

HQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines.

CONCLUSIONS

HQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

摘要

民族药理学相关性

黄芪百合颗粒(HQBHG)是基于传统方剂“黄芪百合粥”和敦煌医学方剂“肉苁蓉汤”改良而成的制剂。该草药除了具有补气滋阴的作用外,还能润肺益肾,是增强对高原缺氧环境适应性的理想选择。

研究目的

本研究旨在探讨黄芪百合颗粒治疗和预防大鼠缺氧性急性肺损伤(ALI)的潜在分子机制。

材料与方法

利用HCP-III实验室动物低压模拟舱模拟高原环境暴露,建立大鼠ALI模型。通过一系列检测评估肺损伤的严重程度,包括肺功能测定、肺干湿比、苏木精-伊红染色和透射电子显微镜检查。采用免疫荧光法测定肺组织中活性氧(ROS)的含量。使用试剂盒测定肺组织中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)和髓过氧化物酶(MPO)的水平。采用酶联免疫吸附测定试剂盒检测血清中促炎细胞因子,包括肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β),以及抗炎细胞因子如白细胞介素-10(IL-10)的水平。利用转录组学鉴定肺组织中的基因表达变化,并通过蛋白质印迹法和定量实时聚合酶链反应测定Toll样受体4(TLR4)/核因子-κB(NF-κB p65)/Nod样受体蛋白3(NLRP3)通路中相关蛋白质和mRNA的相对表达。

结果

结果显示,HQBHG可显著增强肺功能,降低肺干湿比,减轻肺组织损伤,抑制ROS和MDA的形成,并增加SOD活性和GSH表达。研究还表明,HQBHG可抑制肺组织中TLR4/NF-κB p65/NLPR3信号通路的激活,减少下游促炎细胞因子的释放。

结论

HQBHG通过抑制氧化应激和炎症反应,对高原缺氧诱导的ALI具有潜在治疗作用。这表明它可能是一种治疗和预防ALI的新型药物。

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