Department of Pharmacology and Medicinal Chemistry, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, People's Republic of China.
BMC Pulm Med. 2021 Nov 15;21(1):371. doi: 10.1186/s12890-021-01745-7.
Chronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms.
Rat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting.
It showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1.
It indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.
慢性阻塞性肺疾病（COPD）是一种具有气道重塑和气流阻塞特征的慢性肺部疾病。异甘草酸镁（MgIG）是一种用于治疗肝炎的抗炎甘草酸制剂。然而，MgIG 是否可以治疗其他疾病及其作用机制尚不清楚。在这项研究中，我们评估了 MgIG 对 COPD 大鼠的抗炎作用，并探讨了其潜在机制。
通过气管内雾化脂多糖暴露和香烟烟雾诱导构建 COPD 大鼠模型。大鼠随机分为 5 组：对照组、COPD 模型组、沙美特罗氟替卡松对照组、低剂量 MgIG 组和高剂量 MgIG 组。除正常对照组外，其余四组通过香烟烟雾和气管内雾化脂多糖致敏处理构建 COPD 大鼠模型。模型成功建立后，各组 COPD 大鼠每天在暴露于香烟烟雾前，经气管内雾化给予相应剂量的生理盐水、沙美特罗氟替卡松和 MgIG，从第 30 天至第 45 天。正常对照组给予生理盐水。最后，所有大鼠均安乐死。测量肺功能。对支气管肺泡灌洗液中的细胞进行分类，测定炎性因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），通过 HE 染色进行组织病理学分析，并通过 Western blot 测定肺组织中 NLRP3 和裂解的半胱天冬酶-1 的表达。
结果表明，MgIG 治疗（0.40 或 0.80mg/kg/天）可恢复 COPD 大鼠的体重和临床症状，伴有肺炎症浸润减少、气道壁衰减、支气管黏液分泌减少。此外，MgIG 给药减少了 COPD 大鼠支气管肺泡灌洗液中炎性细胞（白细胞、中性粒细胞、淋巴细胞和单核细胞）的积聚，并降低了血清中 IL-6 和 TNF-α的产生。此外，MgIG 治疗还降低了 NLRP3 和裂解的半胱天冬酶-1 的表达水平。
表明 MgIG 可能是 COPD 的一种替代治疗方法，其作用机制可能与抑制 NLRP3 炎性小体有关。
