Huang Jie, Liu Jing, Chang Guangjun, Wang Yan, Ma Nana, Roy Animesh Chadra, Shen Xiangzhen
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
Inflammation. 2021 Dec;44(6):2180-2192. doi: 10.1007/s10753-021-01491-2. Epub 2021 Jun 23.
Bacterial infection is one of the main causes of bovine respiratory disease (BRD), which can cause tremendous losses for the herd farming industry worldwide. L-Glutamine (GLN), a neutral amino acid, has been reported to have anti-inflammatory properties. This study aims to explore the potential protective effects and mechanisms of GLN on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Forty ICR mice were randomly divided into four groups (n = 10): a PBS intratracheal instillation group, a LPS intratracheal instillation group, a GLN gavage group, and a LPS+GLN group (GLN was given 1 h before the LPS stimulation). Twelve hours after LPS administration, the lung tissue and blood were collected. The results showed that the concentrations of IL-6, IL-8, and IL-1β; the protein abundance of the toll-like receptor 4 (TLR4), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated JNK (p-JNK); and the expression level of genes associated with inflammation, such as IL-1β, IL-8, TNF-α, IL-6, TLR4, p38, ERK1/2, and JNK, were significantly increased in the LPS group compared with those in the PBS group. However, these increases were attenuated by GLN pretreatment in the LPS+GLN group. Furthermore, the pathological change of the structure of lung tissue from the LPS group was obvious compared to that from the PBS group; however, with GLN administration, these pathological changes were alleviated. Additionally, the secretion level of mucus and the percentage of positive MUC5AC staining on the epithelial surface area of the airway increased dramatically in the LPS group; however, GLN pretreatment in the LPS+GLN group markedly decreased these phenomena compared with that of the LPS group. These results indicate that GLN supplementation ameliorates LPS-induced ALI in mice and this effect may be mediated by the TLR4/MAPK signaling pathway.
细菌感染是牛呼吸道疾病（BRD）的主要病因之一，可给全球的畜牧业造成巨大损失。L-谷氨酰胺（GLN）是一种中性氨基酸，据报道具有抗炎特性。本研究旨在探讨GLN对小鼠脂多糖（LPS）诱导的急性肺损伤（ALI）的潜在保护作用及机制。将40只ICR小鼠随机分为四组（n = 10）：气管内滴注PBS组、气管内滴注LPS组、GLN灌胃组和LPS + GLN组（在LPS刺激前1小时给予GLN）。给予LPS 12小时后，采集肺组织和血液。结果显示，与PBS组相比，LPS组中白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-1β（IL-1β）的浓度；Toll样受体4（TLR4）、磷酸化p38（p-p38）、磷酸化细胞外信号调节激酶1/2（p-ERK1/2）和磷酸化c-Jun氨基末端激酶（p-JNK）的蛋白丰度；以及与炎症相关基因如IL-1β、IL-8、肿瘤坏死因子-α（TNF-α）、IL-6、TLR4、p38、ERK1/2和JNK的表达水平均显著升高。然而，在LPS + GLN组中，GLN预处理减弱了这些升高。此外，与PBS组相比，LPS组肺组织结构的病理变化明显；然而，给予GLN后，这些病理变化得到缓解。另外，LPS组气道上皮表面积上黏液的分泌水平和MUC5AC阳性染色百分比显著增加；然而，与LPS组相比，LPS + GLN组中的GLN预处理显著降低了这些现象。这些结果表明，补充GLN可改善LPS诱导的小鼠ALI，且这种作用可能由TLR4/丝裂原活化蛋白激酶（MAPK）信号通路介导。
