Luo Zhen, Wang Zeze, Li Ping, Tan Yulong, He Genlin, Liu Xiaoqian, Shen Tingting, Yang Xuesen, Luo Xue
Department of Tropical Medicine, College of Military Preventive Medicine, Army Medical University, Chongqing, China.
Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.
Heliyon. 2023 Nov 4;9(11):e21838. doi: 10.1016/j.heliyon.2023.e21838. eCollection 2023 Nov.
Heatstroke (HS) is a severe acute disease related to gastrointestinal barrier dysfunction, systemic inflammation and multiple organ injury. Many of the functions of Intestinal alkaline phosphatase (IAP) have been linked to gut homeostasis, gut barrier function and inflammation. However, the protective effect of IAP on heatstroke is not fully elucidated. This study aims to explore the protective effect of IAP on heatstroke by maintaining intestinal barrier and improving permeability.
Male C57BL/6 mice were placed in a controlled climate chamber (ambient temperature: 40.0 ± 0.5 °C; humidity: 60 ± 5 %) until the maximum core temperature (Tc, max) reached 42.7 °C (the received criterion of HS). Then heat exposed mice (n = 195) were divided into three groups: 0.2 mL of 0.9 % physiological saline (HS) or vehicle (HS + Vehicle) or 300 IU IAP (HS + IAP) by gavage at 0, 24, and 48 h after onset. Control group mice (Con) (n = 65) were not exposed to heat and were gavaged with 0.9 % physiological saline of the same volume at the same time.
IAP treatment significantly reduced the levels of endotoxin, FD4, and D-lactate in the blood of heatstroke mice, reduced intestinal permeability and maintained the integrity of the intestinal barrier by increasing the expression of tight junction proteins. Meanwhile, IAP treatment alleviated liver and kidney damage caused by heatstroke, reduced serum levels of inflammatory cytokines, and thus improved survival rate of mice after heatstroke.
This study indicates that IAP can improve the intestinal barrier function and intestinal permeability by increasing intestinal tight junctions, reduce systemic inflammation and multiple organ injury and improving the survival rate of heatstroke. Therefore, we consider IAP may be added to enteral nutrition formulas as a potential means for diseases characterized by intestinal permeability disorders, including heatstroke.
中暑（HS）是一种与胃肠屏障功能障碍、全身炎症反应和多器官损伤相关的严重急性疾病。肠碱性磷酸酶（IAP）的许多功能都与肠道内环境稳定、肠道屏障功能及炎症反应有关。然而，IAP对中暑的保护作用尚未完全阐明。本研究旨在通过维持肠道屏障和改善通透性来探究IAP对中暑的保护作用。
将雄性C57BL/6小鼠置于可控气候箱中（环境温度：40.0 ± 0.5°C；湿度：60 ± 5%），直至最高核心体温（Tc, max）达到42.7°C（中暑的既定标准）。然后将受热暴露的小鼠（n = 195）分为三组：在发病后0、24和48小时通过灌胃分别给予0.2 mL 0.9%生理盐水（HS组）或赋形剂（HS + Vehicle组）或300 IU IAP（HS + IAP组）。对照组小鼠（Con）（n = 65）未受热暴露，并在同一时间给予相同体积的0.9%生理盐水灌胃。
IAP治疗显著降低了中暑小鼠血液中的内毒素、FD4和D - 乳酸水平，降低了肠道通透性，并通过增加紧密连接蛋白的表达维持了肠道屏障的完整性。同时，IAP治疗减轻了中暑引起的肝、肾损伤，降低了血清炎症细胞因子水平，从而提高了中暑小鼠的存活率。
本研究表明，IAP可通过增加肠道紧密连接来改善肠道屏障功能和肠道通透性，减轻全身炎症反应和多器官损伤，提高中暑小鼠的存活率。因此，我们认为IAP可能作为一种潜在手段添加到肠内营养配方中，用于治疗包括中暑在内的以肠道通透性障碍为特征的疾病。
