Yi Junfeng, He Genlin, Yang Ju, Luo Zhen, Yang Xuesen, Luo Xue
Cell Physiol Biochem. 2017;41(1):101-114. doi: 10.1159/000455979. Epub 2017 Jan 18.
BACKGROUND/AIMS: The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear.
The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS. The effects of HA on autophagy and lysosomes were assessed in the presence of the autophagy inhibitor 3-methyladenine (3MA). Autophagy and lysosome-associated proteins were analysed by Western blotting.
We found that HA protected against HS-induced death and brain injury. HS can robustly induce autophagy and impair lysosome function. HA pre-conditioning significantly modulated the autophagy level, and improved lysosome function in HS mice. Furthermore, 3MA completely abolished the neuroprotective effect of HA on HS.
HS may induce brain injury through lysosomal dysfunction and impaired autophagic flux. HA protected against HS-induced brain injury via a mechanism involving the autophagy-lysosome pathway.
背景/目的：热适应（HA）在中暑（HS）诱导的脑损伤中的保护作用机制尚不清楚。已知自噬-溶酶体途径在保护应激或患病细胞免于死亡方面发挥重要作用。然而，自噬和溶酶体是否参与HS暴露后HA介导的神经保护作用仍不清楚。
在小鼠遭受HS后，通过直肠温度、苏木精-伊红染色、透射电子显微镜分析、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色和荧光玉髓B染色评估HA的保护作用。在自噬抑制剂3-甲基腺嘌呤（3MA）存在的情况下评估HA对自噬和溶酶体的影响。通过蛋白质印迹分析自噬和溶酶体相关蛋白。
我们发现HA可防止HS诱导的死亡和脑损伤。HS可强烈诱导自噬并损害溶酶体功能。HA预处理可显著调节自噬水平，并改善HS小鼠的溶酶体功能。此外，3MA完全消除了HA对HS的神经保护作用。
HS可能通过溶酶体功能障碍和自噬流受损诱导脑损伤。HA通过涉及自噬-溶酶体途径的机制预防HS诱导的脑损伤。
