Department of Urology, Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Department of Nephrology, Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11880. Epub 2021 Jan 28.
Heat stroke can induce a systemic inflammatory response, which may lead to multi‑organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)‑related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41˚C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro‑positron emission tomography‑computed tomography (micro‑PET/CT), H&E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis‑inducing factor mitochondria‑associated 2 (Aifm2), high‑mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography‑mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro‑PET/CT revealed active metabolism in the whole body of HS mice. H&E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the 'biosynthesis of unsaturated fatty acids' pathway was detected. HS‑associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS‑related AKI.
中暑可引发全身性炎症反应，从而导致多器官功能障碍，包括急性肾损伤（AKI）和电解质紊乱。为了研究中暑（HS）相关 AKI 的发病机制，通过将动物的核心体温升高至 41°C 来诱导 HS 小鼠模型。从尾静脉采集血样，用于测量血浆葡萄糖和肌酐水平。采用微正电子发射断层扫描-计算机断层扫描（micro-PET/CT）、苏木精和伊红（H&E）染色和透射电子显微镜检查小鼠肾脏的代谢和形态变化。进行免疫组化（IHC）和蛋白质印迹分析，以研究凋亡诱导因子线粒体相关 2（Aifm2）、高迁移率族蛋白 1（HMGB1）和晚期糖基化终产物受体（RAGE）的表达。进行液相色谱-质谱分析以寻找差异代谢物和信号通路。成功构建了 HS 小鼠模型，与对照组相比，HS 小鼠血清中肌酐水平显著升高，而 micro-PET/CT 显示 HS 小鼠全身代谢活跃。H&E 和 TUNEL 染色显示 HS 小鼠的肾脏有出血和凋亡的迹象。IHC 和蛋白质印迹分析表明，Aifm2、HMGB1 和 RAGE 显著上调。最后，筛选出 136 个差异代谢物，并检测到“不饱和脂肪酸生物合成”途径的富集。HS 相关 AKI 是全身性炎症反应综合征的肾脏表现，可能由 HMGB1/RAGE 途径触发。代谢组学表明，花生四烯酸、二十二碳六烯酸和二十碳五烯酸的增加可能作为 HS 相关 AKI 的代谢生物标志物。这些发现表明，HMGB1/RAGE 途径与不饱和脂肪酸生物合成之间的相关性可能有助于 HS 相关 AKI 的进展。
