Medical School of Chinese PLA, Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Biochemistry, Graduate School, Chinese PLA General Hospital, Beijing, China.
J Therm Biol. 2021 Oct;101:103081. doi: 10.1016/j.jtherbio.2021.103081. Epub 2021 Aug 18.
Heat stroke is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Mesenchymal stem cells (MSCs) are currently believed to have anti-inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on heat stroke-induced excessive inflammation and neurological dysfunction. We established a heat stroke model in rats under conditions of continuous high temperature and high humidity. After modeling, rats were randomly divided into heat stroke model group, MSCs treatment group and normal temperature control group without any treatment. We performed survival analysis, neurological deficit score, histological staining of hippocampus and cerebellum, immunofluorescence staining of microglia, detection of inflammatory and chemokine levels in the hippocampus and cerebellum in each group. We found that MSCs treatment not only significantly reduced early (day 3) and late (day 28) mortality, but also prominently reduced nerve injury in heat stroke rats, and improved pathology and neuronal cell damage in the hippocampus and cerebellum. In addition, MSCs treatment can significantly inhibit the over-activation of hippocampal microglia in heat stroke rats and the levels of pro-inflammatory factors and chemokines in the hippocampus. Early treatment of MSCs can greatly promote the activation of cerebellar microglia in heat stroke rats. Meanwhile, MSCs treatment has an inhibitory effect on the level of chemokine in the cerebellum of rats in the early stage of heat stroke. In conclusion, the application of MSCs in the treatment of heat stroke in rats can significantly reduce mortality and neurological deficits and improve hippocampal damage, possibly by inhibiting the excessive activation of hippocampal microglia in heat stroke rats.
中暑是一种由高热引起的严重全身炎症反应性疾病,主要表现为神经系统损伤。间充质干细胞(MSCs)目前被认为具有抗炎和免疫调节作用。因此,我们旨在探索 MSCs 对中暑引起的过度炎症和神经功能障碍的保护作用及其机制。我们在持续高温高湿的条件下建立了大鼠中暑模型。建模后,大鼠随机分为中暑模型组、MSCs 治疗组和不做任何处理的常温对照组。我们对各组进行了生存分析、神经功能缺损评分、海马和小脑组织学染色、小胶质细胞免疫荧光染色、海马和小脑炎症和趋化因子水平检测。结果发现,MSCs 治疗不仅显著降低了大鼠的早期(第 3 天)和晚期(第 28 天)死亡率,而且还明显减轻了中暑大鼠的神经损伤,改善了海马和小脑的病理学和神经元细胞损伤。此外,MSCs 治疗还可以显著抑制中暑大鼠海马小胶质细胞的过度激活和海马中促炎因子和趋化因子的水平。早期给予 MSCs 治疗可显著促进中暑大鼠小脑小胶质细胞的激活。同时,MSCs 治疗对中暑大鼠早期小脑趋化因子水平有抑制作用。综上所述,MSCs 在中暑大鼠中的应用可显著降低死亡率和神经功能缺损,改善海马损伤,可能是通过抑制中暑大鼠海马小胶质细胞的过度激活。