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地氟醚通过调节 miR-135b-5p 保护肝脏缺血/再灌注损伤。

Desflurane protects against liver ischemia/reperfusion injury via regulating miR-135b-5p.

机构信息

Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying, China.

出版信息

J Chin Med Assoc. 2021 Jan 1;84(1):38-45. doi: 10.1097/JCMA.0000000000000427.

Abstract

BACKGROUND

A number of anesthetics have protective effect against ischemia-reperfusion (I/R) injury, including desflurane. But the function and molecular mechanism of desflurane in liver I/R injury have not been fully understood. The aim of this study was to investigate the effect of desflurane on liver I/R injury and further investigated the molecular mechanisms involving in miR-135b-5p.

METHODS

The models of liver I/R injury in rats were established, and received desflurane treatment throughout the injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) were measured and compared between groups. H/R-induced cell model in L02 was established, and were treated with desflurane before hypoxia. Quantitative real-time polymerase chain reaction was performed to determine the expression of miR-135b-5p in different groups. The cell apoptosis was detected using flow cytometry assay. Western blot was used for the measurement of protein levels.

RESULTS

I/R significantly increased serum levels of ALT and AST in rats, which were reversed by desflurane treatment. Desflurane also significantly attenuated the increase of cell apoptosis induced by I/R in both vivo and vitro. MiR-135b-5p significantly reversed the protective effect of desflurane against liver I/R injury. Additionally, Janus protein tyrosine kinase (JAK)2 was shown to be a target gene of miR-135b-5p, and miR-135b-5p overexpression significantly decreased the protein levels of p-JAK2, JAK2, p-STAT3.

CONCLUSION

Desflurane attenuated liver I/R injury through regulating miR-135b-5p, and JAK2 was the target gene of mIR-135b-5p. These findings provide references for further development of therapeutic strategies in liver injury.

摘要

背景

许多麻醉剂对缺血再灌注(I/R)损伤具有保护作用,包括地氟醚。但地氟醚在肝 I/R 损伤中的作用及其分子机制尚未完全阐明。本研究旨在探讨地氟醚对肝 I/R 损伤的影响,并进一步探讨涉及 miR-135b-5p 的分子机制。

方法

建立大鼠肝 I/R 损伤模型,并在损伤过程中给予地氟醚治疗。比较各组间血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的变化。用地氟醚预处理缺氧诱导的 L02 细胞模型。采用实时定量聚合酶链反应检测各组 miR-135b-5p 的表达。采用流式细胞术检测细胞凋亡。采用 Western blot 检测蛋白水平。

结果

I/R 显著增加了大鼠血清中 ALT 和 AST 的水平,地氟醚治疗可逆转这一变化。地氟醚还显著减轻了体内和体外 I/R 诱导的细胞凋亡增加。miR-135b-5p 显著逆转了地氟醚对肝 I/R 损伤的保护作用。此外,Janus 蛋白酪氨酸激酶(JAK)2 被证明是 miR-135b-5p 的靶基因,miR-135b-5p 过表达显著降低了 p-JAK2、JAK2、p-STAT3 的蛋白水平。

结论

地氟醚通过调节 miR-135b-5p 减轻肝 I/R 损伤,JAK2 是 miR-135b-5p 的靶基因。这些发现为进一步开发肝损伤的治疗策略提供了参考。

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