Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan, ROC.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Life Sci. 2022 Dec 1;310:121039. doi: 10.1016/j.lfs.2022.121039. Epub 2022 Oct 6.
Heat stroke is a life-threatening disorder triggered by thermoregulatory failure. Hyperthermia-induced splanchnic hypoperfusion has been reported to induce intestinal barrier dysfunction and systemic immune response that ultimately cause multiple-organ failure and death. Intestinal goblet cells contribute greatly to the formation of mucus barrier, which hinders translocation of gut microorganisms. Studies have reported that misoprostol can not only alleviate ischemic injury but also protect GI mucosal layer. Therefore, we evaluated the effects of misoprostol on intestinal goblet cells after heat stress and on multiple-organ dysfunction in heat stroke rats.
Heat stress was established in the heating chamber and followed by misoprostol treatment. Changes in hemodynamics, organ function indices, inflammation, oxidative stress, and survival rate were analyzed. Furthermore, ilea and LS174T cells were used to examine intestinal functions.
Heat stress caused dysfunction of intestinal goblet cells and damage to ilea by increasing oxidative stress and apoptosis. Increased nitrosative stress and inflammation accompanied by hypotension, hypoperfusion, tachycardia, multiple-organ dysfunction, and death were observed in the heat stroke rat model. Treatment of LS174T cells with misoprostol not only decreased oxidative stress and apoptosis but also reduced cytotoxicity caused by heat stress. Moreover, misoprostol prevented disruption of the enteric barrier, multiple-organ injury, and death in rats with heat stroke.
This study indicates that misoprostol could alleviate intestinal damage and organ injury caused by heat stress and be a potential therapy for heat-related illnesses.
中暑是一种由体温调节失败引发的危及生命的疾病。已有研究报道，高温引起的内脏低灌注会导致肠道屏障功能障碍和全身免疫反应，最终导致多器官衰竭和死亡。肠道杯状细胞对黏液屏障的形成有重要贡献，它可以阻止肠道微生物的移位。有研究报道，米索前列醇不仅可以减轻缺血性损伤，还可以保护胃肠道黏膜层。因此，我们评估了米索前列醇在热应激后对肠道杯状细胞的作用以及对中暑大鼠多器官功能障碍的影响。
在加热室内建立热应激模型，然后给予米索前列醇治疗。分析血流动力学、器官功能指标、炎症、氧化应激和存活率的变化。此外，还使用回肠和 LS174T 细胞来检测肠道功能。
热应激通过增加氧化应激和细胞凋亡导致肠道杯状细胞功能障碍和回肠损伤。在中暑大鼠模型中，观察到一氧化氮合酶应激和炎症增加，同时伴有低血压、低灌注、心动过速、多器官功能障碍和死亡。LS174T 细胞用米索前列醇处理不仅降低了氧化应激和细胞凋亡，还减轻了热应激引起的细胞毒性。此外，米索前列醇可预防中暑大鼠肠道屏障破坏、多器官损伤和死亡。
本研究表明，米索前列醇可减轻热应激引起的肠道损伤和器官损伤，是一种治疗与热相关疾病的潜在疗法。
