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microRNA-544 通过靶向 IRAK4 抑制脑缺血再灌注后的炎症反应和细胞凋亡。

MicroRNA-544 inhibits inflammatory response and cell apoptosis after cerebral ischemia reperfusion by targeting IRAK4.

机构信息

Department of Rehabilitation, The First Affiliated Hospital, Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5605-5613. doi: 10.26355/eurrev_201809_15825.

Abstract

OBJECTIVE

Stroke remains the most common malignant cerebrovascular event in the world. The correlation between the expression of miR-544 and the degree of cerebral ischemia reperfusion (CIR) injury has not been well recognized in recent years. This study focuses on the effect of miR-544 on inflammation and apoptosis after CIR.

PATIENTS AND METHODS

Plasma expression of miR-544 in ischemic stroke (IS) patients and healthy controls was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The effects of miR-544 on cerebral infarction and neurological deficits were verified in vitro by tail vein injection of Ago-miR-544. Western blotting was utilized to examine protein expressions of key proteins involving in inflammation and apoptosis in mouse brain. Western blotting, immunofluorescence staining and luciferase assays were used to demonstrate whether miR-544 influences the expression of interleukin-1 receptor-associated kinase 4 (IRAK4), downstream inflammatory and apoptosis-related proteins.

RESULTS

MiR-544 was found decreased in peripheral blood of IS patients compared with healthy controls. MiR-544 has been shown to relieve neurological deficits and reduce the volume of cerebral infarction in mice. Overexpression of miR-544 ameliorated the inflammation and apoptotic responses in brain tissue after ischemia reperfusion by down-regulating the expression of IRAK4, whereas the low expression was opposite in vivo and in vitro.

CONCLUSIONS

We found that miR-544 may participate in controlling inflammation and apoptosis after ischemia-reperfusion by targeting IRAK4, providing possible diagnostic indicators and therapeutic targets for IS.

摘要

目的

中风仍然是世界上最常见的恶性脑血管事件。近年来,miR-544 的表达与脑缺血再灌注(CIR)损伤程度之间的相关性尚未得到很好的认识。本研究重点研究了 miR-544 对 CIR 后炎症和细胞凋亡的影响。

患者和方法

通过定量逆转录聚合酶链反应(qRT-PCR)测定缺血性中风(IS)患者和健康对照者血浆中 miR-544 的表达。通过尾静脉注射 Ago-miR-544 ,在体外验证 miR-544 对脑梗死和神经功能缺损的影响。利用 Western blot 检测小鼠脑组织中涉及炎症和细胞凋亡的关键蛋白的表达。Western blot、免疫荧光染色和荧光素酶报告基因实验用于证明 miR-544 是否影响白细胞介素 1 受体相关激酶 4(IRAK4)、下游炎症和凋亡相关蛋白的表达。

结果

与健康对照组相比,IS 患者外周血中 miR-544 表达降低。miR-544 可减轻小鼠神经功能缺损和脑梗死体积。miR-544 的过表达通过下调 IRAK4 的表达减轻缺血再灌注后脑组织的炎症和细胞凋亡反应,而体内和体外的低表达则相反。

结论

我们发现 miR-544 可能通过靶向 IRAK4 参与控制缺血再灌注后的炎症和细胞凋亡,为 IS 提供了可能的诊断指标和治疗靶点。

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