Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China.
Department of Pediatrics, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.
J Physiol Biochem. 2023 Aug;79(3):613-623. doi: 10.1007/s13105-023-00961-5. Epub 2023 May 5.
Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln's effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln's function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway.
谷氨酰胺（Gln）是体内作用最广泛、含量最丰富的氨基酸，具有抗炎作用，调节机体代谢，提高免疫功能。然而，Gln 对新生大鼠高氧性肺损伤的作用机制尚不清楚。因此，本工作重点研究 Gln 对高氧诱导的新生大鼠肺损伤的作用及其机制。我们检测了新生大鼠的体重和肺组织湿重/干重比。进行苏木精-伊红（HE）染色，以观察肺组织的组织病理学改变。此外，采用酶联免疫吸附试验（ELISA）检测支气管肺泡灌洗液（BALF）中促炎细胞因子的水平。采用 TUNEL 检测法观察肺组织细胞的凋亡情况。采用 Western blot 检测内质网应激（ERS）相关蛋白水平。结果表明，Gln 促进了新生大鼠的体重增长，显著减轻了肺组织的病理损伤和氧化应激，改善了肺功能。Gln 减少了 BALF 中促炎细胞因子的释放和炎性细胞的产生，抑制了肺组织细胞的凋亡。此外，我们发现 Gln 可以下调 ERS 相关蛋白水平（GRP78、Caspase-12、CHOP），并抑制 c-Jun N-末端激酶（JNK）和肌醇需求酶 1α（IRE1α）的磷酸化。这些在支气管肺发育不良（BPD）动物模型中的结果表明，Gln 通过减轻肺炎症、氧化应激和凋亡，改善肺功能，可能对 BPD 具有治疗作用；其作用机制可能与抑制 IRE1α/JNK 通路有关。
