Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke
Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke
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中暑后肺部炎症反应和氧化应激相关基因的表达谱
DOI：
10.1042/bsr20192048
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发表时间：
2020-06-05
影响因子：
4
通讯作者：
Yi, Gao
中科院分区：
文献类型：
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作者：
Liu, Zhaoyu;Chen, Jitao;Yi, Gao
背景：中暑（HS）是一种由高温引起的身体功能失调疾病。肺作为重要的气体交换和散热器官，往往首当其冲。HS引起的肺损伤会损害肺的通气功能，进而对其他组织器官造成损伤。然而，中暑肺损伤的具体机制尚不清楚。方法：取对照组大鼠肺组织和HS模型大鼠肺组织。通过高通量测序鉴定基因表达谱。deg用R计算，qRT-PCR验证。使用差异表达基因（DEGs）进行基因本体（GO）、京都基因与基因组百科全书（KEGG）和细胞富集。最后，采用H&E染色进行肺组织病理学检查。结果：共鉴定出471个基因为deg，其中257个基因上调，214个基因下调。qRT-PCR验证了上调和下调最多的deg，证实了表达趋势。GO、KEGG和蛋白-蛋白相互作用（PPI）网络分析显示，DEGs在白细胞迁移、脂多糖应答、NIK/NF-kappaB信号、活性氧应答和热应答中显著富集，中心基因为Tnf、Il1b、Cxcl2、Ccl2、Mmp9、Timp1、Hmox1、Serpine1、Mmp8和Csf1，其中大部分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显示单核细胞、巨核细胞和巨噬细胞在热应激反应中富集。结论：本研究确定了热应激后肺的关键基因、信号通路和浸润细胞类型，将加深我们对热应激转录反应的认识，并可能为热应激的治疗提供新的思路。
Abstract Background: 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. Methods: 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. Results: 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. Conclusions: 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.