甘草酸二铵减轻肺结核模型大鼠肺损伤

doi:10.16352/j.issn.1001-6325.2024.11.1544

摘要/Abstract

摘要： 目的探讨甘草酸二铵(DG)对肺结核模型大鼠肺损伤的影响。方法构建肺结核大鼠模型,将造模成功大鼠随机分为模型组(model组)、甘草酸二铵低、中、高剂量组(L-DG、M-DG、H-DG组)、甘草酸二铵高剂量+过氧化物酶体增殖物激活受体γ(PPARγ)抑制剂组(H-DG+GW9662组),另取18只作为对照组(control组);检测肺组织结核分枝杆菌(Mtb)菌落数;HE染色检测肺组织病理学变化;TUNEL检测肺组织细胞凋亡;ELISA检测血清炎性因子水平;Western blot检测肺组织PPARγ、磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)/p38丝裂原活化蛋白激酶(p38MAPK)表达。结果模型组较对照组肺组织结构破坏严重,产生大量增生型结核结节,肺泡形态发生变化,炎性细胞浸润明显,甚至出现干酪样坏死现象,结核菌菌落数增多,细胞凋亡率、TNF-α、IL-6、IFN-γ、COX-2水平及p-p38MAPK/p38MAPK表达升高,PPARγ表达降低(P＜0.05)。L-DG、M-DG、H-DG组较模型组肺组织结构、肺泡形态、炎性细胞浸润、干酪样坏死等现象均有所改善,结核菌菌落数减少,细胞凋亡率降低,TNF-α、IL-6、IFN-γ、COX-2水平及p-p38MAPK/p38MAPK表达降低,PPARγ表达升高,其中H-DG组变化最显著(P＜0.05)。GW9662处理可部分逆转DG对肺结核大鼠的肺损伤改善作用。结论 DG可改善肺结核大鼠的肺损伤,其作用机制可能与激活PPARγ/p38MAPK通路有关。

关键词: 甘草酸二铵, 过氧化物酶体增殖物激活受体γ/p38丝裂原活化蛋白激酶通路, 肺结核, 肺损伤

Abstract: Objective To investigate the effect of diammonium glycyrrhizinate (DG) on pulmonary injury of rats with pulmonary tuberculosis. Methods The rat models of pulmonary tuberculosis were constructed and then the animals were randomly divided into model group, diammonium glycyrrhizinate treatment groups (low-dose, medium-dose and high-dose) groups, high dose of diammonium glycyrrhizinate plus peroxisome proliferator-activated receptor γ(PPARγ) inhibitor group (H-DG+GW9662 group), and another 18 rats were selected as control group. The colony count of Mycobacterium tuberculosis(Mtb) in lung tissue was detected. HE staining microscopy was applied to detect lung histopathology. TUNEL was applied to detect apoptosis of lung tissue cells. ELISA was applied to detect serum level of inflammatory factors. Western blot was applied to measure PPARγ, phosphorylated p38 mitogen-activated protein kinase(p-p38MAPK) and p38 mitogen-activated protein kinase (p38MAPK) in lung tissue. Results Compared with the control group, the lung tissue structure in model group was severely damaged with a large number of proliferative tuberculosis nodules, changes of alveolar morphology, inflammatory cell infiltration and even caseous necrosis were found, and the number of tuberculosis colonies, apoptosis rate, TNF-α, IL-6, IFN-γ, COX-2 levels, and p-p38MAPK/p38MAPK expression were all increased, while PPARγ expression was decreased(P＜0.05). In L-DG, M-DG, H-DG groups improvement of lung tissue structure, alveolar morphology, inflammatory cell infiltration, and caseous necrosis were found as compared to the model group, while the counting number of tuberculosis colonies decreased and rate of cell apoptosis decreased. The level of TNF-α, IL-6, IFN-γ, COX-2 and expression of p-p38MAPK/p38MAPK reduced, the expression of PPARγ all increased. The H-DG group showed the most significant changes(P＜0.05). GW9662 treatment significantly reversed the improvement of DG on pulmonary injury in rats with pulmonary tuberculosis. Conclusions DG improves lung injury in rats with pulmonary tuberculosis and its mechanism is potentially related to the activation of PPARγ pathway and inhibition of p38MAPK pathway.

Key words: diammonium glycyrrhizinate, peroxisome proliferators-activated receptor γ/p38 mitogen-activated protein kinase pathway, pulmonary tuberculosis, lung injury

中图分类号:

R521.9

曹培谦, 王志刚, 苗学红. 甘草酸二铵减轻肺结核模型大鼠肺损伤[J]. 基础医学与临床, 2024, 44(11): 1544-1550.

CAO Peiqian, WANG Zhigang, MIAO Xuehong. Diammonium glycyrrhizinate alleviates lung injury in rat models with lung tuberculosis[J]. Basic & Clinical Medicine, 2024, 44(11): 1544-1550.

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