Ahmed Rasha F, Moussa Rabab A, Eldemerdash Reda S, Zakaria Mahmoud M, Abdel-Gaber Seham A
Department of Medical Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Department of Pathology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Iran J Basic Med Sci. 2019 Dec;22(12):1483-1492. doi: 10.22038/IJBMS.2019.14069.
Aspiration is a common cause of acute lung injury (ALI), which lacks an effective treatment. Inflammation and oxidative stress play key roles in ALI development. Silymarin is an active extract of Silybum marianum plant seeds (milk thistle). Silymarin has potent anti-inflammatory and antioxidant effects; however its role in aspiration induced ALI has not been investigated. The aim of this study is to investigate the role of silymarin in the treatment of hydrochloric acid (HCl) aspiration induced ALI and explores its mechanisms of action.
The study included three groups of rats: Control non-treated group, ALI group (intra-tracheal HCl injected), and silymarin treated ALI group. White blood cells (WBCs) with differential count, oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), transforming growth factor-beta (TGF-β), cyclooxygenase 2 (COX-2), nuclear factor erythroid 2-related factor-2 (Nrf-2), and heme oxygenase-1 (HO-1) were investigated. Lung tissue histopathology and immunohistochemical expression of survivin and proliferating cell nuclear antigen (PCNA) were also examined.
The results of the study showed that HCL caused histopathological changes in ALI with leukocytopenia and increased oxidative stress biomarkers. It increased TGF-β, up-regulated mRNA expression of COX-2, Nrf-2, and HO-1 and increased survivin and PCNA but decreased Bcl-2. Silymarin ameliorated the histopathological lung injury with further up-regulation of Nrf-2 and HO-1 mRNA and decreased the inflammatory and fibrotic parameters together with up-regulation of the anti-apoptotic and the proliferation parameters.
The protective effect of silymarin against ALI is mediated by Nrf-2/HO-1 pathway with subsequent antioxidant, anti-inflammatory, antiapoptotic, and proliferating activities.
误吸是急性肺损伤（ALI）的常见病因，目前缺乏有效治疗方法。炎症和氧化应激在ALI的发生发展中起关键作用。水飞蓟素是水飞蓟植物种子（奶蓟）的活性提取物。水飞蓟素具有强大的抗炎和抗氧化作用；然而，其在误吸诱导的ALI中的作用尚未得到研究。本研究旨在探讨水飞蓟素在治疗盐酸（HCl）误吸诱导的ALI中的作用，并探索其作用机制。
本研究包括三组大鼠：对照组（未处理）、ALI组（气管内注射HCl）和水飞蓟素治疗的ALI组。检测白细胞（WBC）及其分类计数、氧化应激参数、B细胞淋巴瘤2（Bcl-2）、转化生长因子-β（TGF-β）、环氧化酶2（COX-2）、核因子红细胞2相关因子2（Nrf-2）和血红素加氧酶-1（HO-1）。还检查了肺组织的组织病理学以及生存素和增殖细胞核抗原（PCNA）的免疫组化表达。
研究结果表明，HCl导致ALI出现组织病理学变化，伴有白细胞减少和氧化应激生物标志物增加。它增加了TGF-β，上调了COX-2、Nrf-2和HO-1的mRNA表达，增加了生存素和PCNA，但降低了Bcl-2。水飞蓟素改善了肺组织病理学损伤，进一步上调了Nrf-2和HO-1 mRNA，并降低了炎症和纤维化参数，同时上调了抗凋亡和增殖参数。
水飞蓟素对ALI的保护作用是通过Nrf-2/HO-1途径介导的，随后具有抗氧化、抗炎、抗凋亡和增殖活性。
