MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline
MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline
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MicroRNA文件在富氢盐水预防肠道缺血/再灌注损伤中的应用
DOI：
10.1042/bsr20191043
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发表时间：
2019-12
影响因子：
4
通讯作者：
Huang Pinjie
中科院分区：
文献类型：
--
作者：
Yao Weifeng;Lin Xiaoyu;Han Xue;Zeng Lanfen;Guo Anshun;Guan Yu;Hei Ziqing;Liu Jianpei;Huang Pinjie
摘要背景：富氢盐水（HRS）已被证明对缺血/再灌注（I/R）损伤有效。然而，对潜在信号事件的了解仍然很少。最近研究发现microRNAs （miRNAs）介导肠道I/R损伤，我们推测HRS可能通过调节miRNAs来保护肠道免受I/R损伤。方法：小鼠腹腔注射生理盐水或HRS，每天1次，连续5天，然后进行60 min缺血后180 min肠系膜上动脉再灌注的肠I/R。收集小肠进行组织病理学分析、miRNA微阵列分析、Real-Time PCR和Western blotting。接下来，将miR-199a-3p模拟物或抑制剂转染到IEC-6细胞中，以探索HRS治疗与miR-199a-3p之间的关系。结果：HRS预处理可减轻I/ r诱导的粘膜损伤和上皮细胞凋亡。通过HRS预处理，共有64个肠道I/ r反应性mirna发生了显著改变，其中我们通过Real-Time PCR验证了四个具有最高显著性的新型mirna，即miR-199a-3p， miR-296-5p， miR-5126和miR-6538。特别是miR-199a-3p在I/R下显著升高，而在HRS下降低。计算分析预测，胰岛素样生长因子(IGF)-1、哺乳动物雷帕霉素靶点（mTOR）和磷酸肌醇激酶（PI3K）调控亚基1是miR-199a-3p的靶标，表明参与促生存途径IGF- 1/PI3K/Akt/mTOR。在体外实验中，HRS处理降低了miR-199a-3p水平，增加了IGF-1、PI3K和mTOR mRNA的表达，恢复了IEC-6细胞的活力，而这种保护作用在miR-199a-3p模拟物处理下被逆转。结论：综上所述，miR-199a-3p可能在HRS的抗凋亡机制中发挥关键作用，有助于保护肠道免受I/R损伤。
Abstract Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by Real-Time PCR, namely miR-199a-3p, miR-296-5p, miR-5126, and miR-6538. Particularly, miR-199a-3p was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF- 1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.
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