He Xuegang, Deng Bo, Ma Miao, Wang Keyao, Li Ying, Wang Yonggang, Kang Xuewen
Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China; The International Cooperation Base of Gansu Province for the Pain Research in Spinal Disorders, Lanzhou, China.
Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
World Neurosurg. 2023 Sep;177:e332-e342. doi: 10.1016/j.wneu.2023.06.043. Epub 2023 Jun 20.
Programmed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies.
We downloaded the rats' SCI expression matrix GSE45006, and the ssGSEA method was used to analyze the PCD after SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction, and HUB genes were identified. Finally, the correlation between HUB genes and PCD was analyzed.
Apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy increased significantly in acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury, and autophagy.
PCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, and ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related HUB genes may be the therapeutic target of SCI.
脊髓损伤（SCI）发展过程中的程序性细胞死亡（PCD）较为复杂，包括凋亡、坏死性凋亡、焦亡、铁死亡、铜死亡和自噬。明确SCI后PCD的表达水平及潜在分子靶点对于制定相关治疗策略很有必要。
我们下载了大鼠SCI表达矩阵GSE45006，并采用单样本基因集富集分析（ssGSEA）方法分析SCI后的PCD。然后鉴定相关差异表达基因（DEGs），并进行基因本体（GO）和通路分析、蛋白质-蛋白质相互作用（PPI）网络构建以及鉴定枢纽基因。最后分析枢纽基因与PCD之间的相关性。
急性SCI中凋亡、坏死性凋亡、焦亡、铁死亡和自噬显著增加，然后在亚急性和慢性阶段逐渐下降；急性SCI中的铜死亡显著下降，然后逐渐增加。此外，我们还在SCI发展过程中筛选出116个DEGs。GO和通路分析表明DEGs与有丝分裂和细胞周期有关。鉴定出的枢纽基因与损伤后的细胞凋亡、坏死性凋亡、焦亡、铁死亡以及自噬密切相关。
PCD在SCI后的不同阶段表现不同。抑制损伤后的凋亡、坏死性凋亡、焦亡和铁死亡并诱导自噬可能是治疗策略。此外，基于相关枢纽基因的干预治疗可能是SCI的治疗靶点。
