State Key Laboratory of Animal Nutrition, Department of Animal Science and Feed Science, China Agricultural University, Beijing, China.
State Key Laboratory of Animal Nutrition, Department of Animal Science and Feed Science, China Agricultural University, Beijing, China.
J Nutr Biochem. 2021 Mar;89:108557. doi: 10.1016/j.jnutbio.2020.108557. Epub 2020 Nov 26.
Acute lung injury has been reported to be associated with heat stress in various animals. Ursolic acid is a natural pentacyclic triterpenoid compound with multiple bioactivities. However, it remains unknown whether ursolic acid supplementation alleviates heat stress-induced lung injury. In the present study, male Institute of Cancer Research mice were left untreated under a normal temperature condition (23±1°C), receiving orally administrated with vehicle (phosphate buffered saline) or ursolic acid (40 mg/kg BW·d for 2 d), and then were subjected to high temperature (41±1°C) for 2 h. Histological alterations, activities of antioxidative enzymes, apoptosis, generation of reactive oxygen species, abundance of inflammatory cytokines, and endoplasmic reticulum stress-related proteins were analyzed. Compared with the controls, heat stress treatment led to enhanced apoptosis, increased HO production, and upregulated protein levels of inflammatory cytokines in the serum, including tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta. Activities of malondialdehyde, lactate dehydrogenase, and myeloperoxidase were increased, while the activities for superoxide dismutase and catalase were reduced in lung tissues of mice. All these alterations were significantly prevented by ursolic acid administration. Further study showed that heat stress led to activation of protein kinase-like ER kinase eukaryotic initiation factor 2 alpha -the transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) signaling, which was attenuated by ursolic acid supplementation. These findings indicated that ursolic acid pretreatment protected lung tissues against heat stress-induced injury by regulating inflammatory cytokines and unfolded protein response in mice. Ursolic acid supplementation might be a therapeutic strategy to alleviate high temperature-induced lung injury in humans and animals.
急性肺损伤已被报道与各种动物的热应激有关。熊果酸是一种具有多种生物活性的天然五环三萜化合物。然而，熊果酸补充剂是否能缓解热应激引起的肺损伤仍不清楚。在本研究中，雄性 Institute of Cancer Research 小鼠在正常温度条件下（23±1°C）未经处理，口服给予 vehicle（磷酸盐缓冲盐水）或熊果酸（40 mg/kg BW·d，连续 2 天），然后暴露于高温（41±1°C）2 小时。分析了组织学改变、抗氧化酶活性、细胞凋亡、活性氧生成、炎症细胞因子丰度和内质网应激相关蛋白。与对照组相比，热应激处理导致细胞凋亡增强，HO 生成增加，血清中炎症细胞因子（包括肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β）的蛋白水平上调。丙二醛、乳酸脱氢酶和髓过氧化物酶的活性增加，而肺组织中超氧化物歧化酶和过氧化氢酶的活性降低。熊果酸给药显著预防了所有这些变化。进一步的研究表明，热应激导致蛋白激酶样内质网激酶真核起始因子 2α-CCAAT 增强子结合蛋白同源蛋白（CHOP）信号转导的激活，而熊果酸补充则减弱了这种激活。这些发现表明，熊果酸预处理通过调节炎症细胞因子和未折叠蛋白反应，保护小鼠肺组织免受热应激引起的损伤。熊果酸补充可能是缓解人和动物高温引起的肺损伤的一种治疗策略。
