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LncRNA SNHG7 敲低通过调节 miR-34a-5p/YWHAG 轴加重失血性休克孕鼠肝缺血再灌注损伤并促进细胞凋亡。

LncRNA SNHG7 Knockdown Aggravates Hepatic Ischemia-Reperfusion Injury and Promotes Apoptosis in Hemorrhagic Shock Pregnant Rats by Modulating miR-34a-5p/YWHAG Axis.

机构信息

Department of Obstetrics and Gynecology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213000, China.

Department of Obstetrics and Gynecology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, 213000, China.

出版信息

Mol Biotechnol. 2023 Jun;65(6):983-996. doi: 10.1007/s12033-022-00613-x. Epub 2022 Nov 24.

Abstract

Hemorrhagic shock is a frequent threat to pregnant women, and blood transfusions can contribute to organ damage, including hepatic ischemia-reperfusion (HIR) injury. LncRNA SNHG7 (SNHG7) has been reported to exert an essential role in various diseases, while the effect of SNHG7 on HIR injury induced by hemorrhagic shock and reperfusion in pregnant rats is still unclear. In our study, we examined the function and mechanism of SNHG7 in the progression of HIR injury in pregnant rats. The results showed that SNHG7 expression was low in the hepatic tissues of pregnant rats after the hemorrhagic shock and reperfusion modeling. Knockdown of SNHG7 further aggravated hepatic injury, apoptosis, and oxidative stress induced by hemorrhagic shock and reperfusion during pregnancy. Additionally, SNHG7 was bound directly to miR-34a-5p, and miR-34a-5p inhibitors partially reversed the effect of SNHG7 silencing on models of hemorrhagic shock and reperfusion. Furthermore, YWHAG is a direct target of miR-34a-5p and is negatively regulated by miR-34a-5p mimics. Overexpression of YWHAG effectively eliminated the effect of SNHG7 knockdown on pregnant rats. In summary, this investigation proved that SNHG7 knockdown exacerbated HIR injury after hemorrhagic shock in pregnant rats, and reperfusion might by mediating miR-34a-5p/YWHAG axis, indicating that SNHG7 can serve as a target gene for the treatment of HIR injury caused by hemorrhagic shock and reperfusion during pregnancy.

摘要

失血性休克是孕妇经常面临的威胁,输血可能导致器官损伤,包括肝缺血再灌注(HIR)损伤。LncRNA SNHG7(SNHG7)已被报道在各种疾病中发挥重要作用,而 SNHG7 对失血性休克和再灌注引起的孕鼠 HIR 损伤的影响尚不清楚。在本研究中,我们研究了 SNHG7 在孕鼠 HIR 损伤进展中的作用和机制。结果表明,失血性休克和再灌注建模后孕鼠肝组织中 SNHG7 表达降低。SNHG7 敲低进一步加重了孕鼠失血性休克和再灌注引起的肝损伤、细胞凋亡和氧化应激。此外,SNHG7 直接与 miR-34a-5p 结合,miR-34a-5p 抑制剂部分逆转了 SNHG7 沉默对失血性休克和再灌注模型的影响。此外,YWHAG 是 miR-34a-5p 的直接靶基因,受 miR-34a-5p 模拟物的负调控。YWHAG 的过表达有效消除了 SNHG7 敲低对孕鼠的影响。综上所述,本研究证明 SNHG7 敲低可加重失血性休克和再灌注后孕鼠 HIR 损伤,可能通过介导 miR-34a-5p/YWHAG 轴,表明 SNHG7 可作为治疗失血性休克和再灌注引起的孕鼠 HIR 损伤的靶基因。

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