Department of Center Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
Department of Respiratory Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20192048.
Heat stroke (HS) is a physically dysfunctional illness caused by hyperthermia. Lung, as the important place for gas-exchange and heat-dissipation organ, is often first to be injured. Lung injury caused by HS impairs the ventilation function of lung, which will subsequently cause damage to other tissues and organs. Nevertheless, the specific mechanism of lung injury in heat stroke is still unknown.
Rat lung tissues from controls or HS models were harvested. The gene expression profile was identified by high-throughput sequencing. DEGs were calculated using R and validated by qRT-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and cell-enrichment were performed using differential expression genes (DEGs). Finally, lung histopathology was accessed by H&E staining.
About 471 genes were identified to be DEGs, of which 257 genes were up-regulated, and 214 genes were down-regulated. The most up-regulated and down-regulated DEGs were validated by qRT-PCR, which confirmed the tendency of expression. GO, KEGG, and protein-protein interaction (PPI)-network analyses disclosed DEGs were significantly enriched in leukocyte migration, response to lipopolysaccharide, NIK/NF-kappaB signaling, response to reactive oxygen species, response to heat, and the hub genes were Tnf, Il1b, Cxcl2, Ccl2, Mmp9, Timp1, Hmox1, Serpine1, Mmp8 and Csf1, most of which were closely related to inflammagenesis and oxidative stress. Finally, cell-enrichment analysis and histopathologic analysis showed Monocytes, Megakaryotyes, and Macrophages were enriched in response to heat stress.
The present study identified key genes, signal pathways and infiltrated-cell types in lung after heat stress, which will deepen our understanding of transcriptional response to heat stress, and might provide new ideas for the treatment of HS.
中暑（HS）是一种由体温过高引起的身体机能障碍性疾病。肺作为气体交换和散热器官，通常是第一个受到损伤的器官。HS 引起的肺损伤会损害肺的通气功能，进而导致其他组织和器官受损。然而，中暑导致肺损伤的确切机制仍不清楚。
采集对照组和 HS 模型大鼠的肺组织。通过高通量测序鉴定基因表达谱。使用 R 计算差异表达基因（DEGs），并通过 qRT-PCR 进行验证。使用差异表达基因进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）和细胞富集分析。最后，通过 H&E 染色评估肺组织病理学。
共鉴定出约 471 个 DEGs，其中 257 个基因上调，214 个基因下调。通过 qRT-PCR 验证了最上调和下调的 DEGs，验证了表达趋势。GO、KEGG 和蛋白质-蛋白质相互作用（PPI）网络分析表明，DEGs 显著富集于白细胞迁移、脂多糖反应、NIK/NF-κB 信号、活性氧反应、热反应，枢纽基因包括 Tnf、Il1b、Cxcl2、Ccl2、Mmp9、Timp1、Hmox1、Serpine1、Mmp8 和 Csf1，其中大多数与炎症发生和氧化应激密切相关。最后，细胞富集分析和组织病理学分析表明，单核细胞、巨核细胞和巨噬细胞在热应激时被富集。
本研究鉴定了热应激后肺中关键基因、信号通路和浸润细胞类型，加深了我们对热应激转录反应的理解，为中暑的治疗提供了新的思路。
