Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar-243122, Bareilly, Uttar Pradesh, India.
Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar-243122, Bareilly, Uttar Pradesh, India.
Cytokine. 2018 Oct;110:333-343. doi: 10.1016/j.cyto.2018.03.042. Epub 2018 Apr 11.
The present investigation was undertaken to assess the result of pretreatment of luteolin in sepsis-induced acute lung injury in mice and its mechanism of action. Luteolin was administered intraperitoneally one hour before caecal ligation and puncture (CLP) surgery in mice. Acute lung injury was assessed by estimation of different parameters like lung edema, protein content, cytokines level, oxidative stress, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule (ICAM)-1 expression and histopathology. Pretreatment of mice with luteolin showed decrease lung edema and protein content in tissue and bronchoalveolar lavage fluid (BALF). However, mice pretreated with luteolin showed reduction (p = 0.92) in blood and lung tissue bacterial counts however it was non significant. Further, luteolin showed significant reduction in interleukin (IL)-6 and IL-1β in lung tissue which are the proinflammatory cytokines. However, plasma IL-1β and tissue tumor necrosis factor (TNF)-α level decrease (p = 0.24; p = 0.19) with this pretreatment. Further, ICAM-1 mRNA expression and nuclear factor (NF)-kappa B protein expression were significantly (p < 0.01) decreased in luteolin pretreated septic mice. The lung iNOS level, iNOS mRNA and protein expressions were markedly (p = 0.25; p = 0.50; p = 0.06) altered with luteolin pretreatment, respectively. Also, significant reduction in lipid peroxidation and increase in the activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase was noted with luteolin pretreatment. However, luteolin did not alter (p = 0.36) the non enzymatic antioxidant GSH activity in septic mice. Histopathology of lung tissue showed reduction in lung injury with the luteolin pretreatment in septic mice. The study suggests that luteolin showed attenuation in sepsis-induced acute lung injury in mice through suppression in ICAM-1, NF-kappa B, oxidative stress and partially iNOS pathways.
本研究旨在评估预处理木樨草素对盲肠结扎穿孔（CLP）诱导的小鼠脓毒症性急性肺损伤的效果及其作用机制。在 CLP 手术前 1 小时，通过腹腔内给予木樨草素处理小鼠。通过估计肺水肿、蛋白含量、细胞因子水平、氧化应激、诱导型一氧化氮合酶（iNOS）、细胞间黏附分子（ICAM）-1 表达和组织病理学等不同参数来评估急性肺损伤。用木樨草素预处理小鼠可降低肺组织和支气管肺泡灌洗液（BALF）中的水肿和蛋白含量。然而，用木樨草素预处理的小鼠血液和肺组织的细菌计数减少（p=0.92），但无统计学意义。此外，木樨草素可显著降低肺组织中的白细胞介素（IL）-6 和 IL-1β，这些是促炎细胞因子。然而，这种预处理使血浆 IL-1β 和组织肿瘤坏死因子（TNF）-α水平降低（p=0.24；p=0.19）。此外，在脓毒症小鼠中，木樨草素预处理可显著降低 ICAM-1 mRNA 表达和核因子（NF）-kappa B 蛋白表达（p<0.01）。肺 iNOS 水平、iNOS mRNA 和蛋白表达分别与木樨草素预处理明显改变（p=0.25；p=0.50；p=0.06）。此外，用木樨草素预处理还可显著降低脂质过氧化，增加超氧化物歧化酶（SOD）和过氧化氢酶等抗氧化酶的活性。然而，木樨草素并未改变脓毒症小鼠中非酶抗氧化剂 GSH 的活性（p=0.36）。肺组织的组织病理学显示，在脓毒症小鼠中用木樨草素预处理可减轻肺损伤。该研究表明，木樨草素通过抑制 ICAM-1、NF-kappa B、氧化应激和部分 iNOS 途径，可减轻 CLP 诱导的小鼠脓毒症性急性肺损伤。
