Hua Yongliang, Xu Yanan, Li Xinglong, Yin Bing, Lu Shounan, Wang Chaoqun, Ke Shanjia, Qian Baolin, Yu Hongjun, Bai Miaoyu, Ma Yong
Department of Pediatric Surgery, The Sixth Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang, China; Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang, China.
Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang, China.
Biochem Biophys Res Commun. 2022 Oct 30;627:30-38. doi: 10.1016/j.bbrc.2022.08.041. Epub 2022 Aug 18.
The objective of our study was to elucidate the possible underlying mechanism for the protective effect of ischaemic preconditioning (IPC) against ischaemia-reperfusion (I/R) injury and to provide new research perspectives of long non-coding RNAs (lncRNAs). In this study, serum and liver tissue samples were collected to measure indexes of liver injury from a mouse liver model in sham, I/R injury and I/R + IPC groups. Furthermore, liver samples from 5 randomly selected mice per group were extracted and subjected to the microarray and subsequent bioinformatics analysis. IPC ameliorated liver damage by lowered liver transaminase levels and pro-inflammatory cytokines. A total of 167 lncRNAs and 108 messenger RNAs (mRNAs) were significantly differentially expressed genes (DEGs) between the I/R + IPC and I/R groups. Gene Ontology (GO) analysis revealed that these genes were mainly related to unfolded proteins, responses to topologically incorrect proteins, responses to temperature stimuli, protein folding and protein refolding. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated that the DEGs were enriched in the following pathways: protein processing in the endoplasmic reticulum; antigen processing and presentation; and fructose and mannose metabolism. Additionally, the 7 selected DEGs (Hspa1ab, Chka, Clec2h, Mvd, Adra1a, AK085737 and AK088966) were validated in modules of the lncRNA-mRNA weighted coexpression network, which agreed with the qRT-PCR and chip data. And the identified differentially expressed lncRNAs and mRNAs may provide new clues to understand the pivotal pathophysiological mechanism by which IPC alleviates I/R-caused liver damage.
我们研究的目的是阐明缺血预处理（IPC）对缺血再灌注（I/R）损伤具有保护作用的潜在机制，并提供长链非编码RNA（lncRNA）的新研究视角。在本研究中，收集了假手术组、I/R损伤组和I/R + IPC组小鼠肝脏模型的血清和肝组织样本，以检测肝损伤指标。此外，从每组中随机选取5只小鼠的肝脏样本进行提取，并进行微阵列及后续生物信息学分析。IPC通过降低肝转氨酶水平和促炎细胞因子改善了肝损伤。I/R + IPC组与I/R组之间共有167个lncRNA和108个信使RNA（mRNA）为显著差异表达基因（DEG）。基因本体论（GO）分析显示，这些基因主要与未折叠蛋白、对拓扑错误蛋白的反应、对温度刺激的反应、蛋白质折叠和蛋白质重折叠有关。京都基因与基因组百科全书（KEGG）通路分析表明，DEG在以下通路中富集：内质网中的蛋白质加工；抗原加工和呈递；以及果糖和甘露糖代谢。此外，并在lncRNA-mRNA加权共表达网络模块中验证了7个选定的DEG（Hspa1ab、Chka、Clec2h、Mvd、Adra1a、AK085737和AK088966），这与qRT-PCR和芯片数据一致。并且鉴定出的差异表达lncRNA和mRNA可能为理解IPC减轻I/R所致肝损伤的关键病理生理机制提供新线索。
