Protective Effect of miR-340-5p against Brain Injury after Intracerebral Hemorrhage by Targeting PDCD4

医学 脑出血 促炎细胞因子 下调和上调 体内 肿瘤坏死因子α 小RNA 胶原酶 炎症 药理学 免疫学 内科学 基因 生物 生物化学 蛛网膜下腔出血 生物技术
作者
Wei Zhou,Guandong Huang,Jueming Ye,Jiamei Jiang,Qing Xu
出处
期刊:Cerebrovascular Diseases [S. Karger AG]
卷期号:49 (6): 593-600 被引量:16
标识
DOI:10.1159/000508210
摘要

<b><i>Objective:</i></b> Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. Increasing evidence has documented the crucial role of microRNAs in ICH. The present study aimed to investigate the role and underlying mechanism of miR-340-5p in ICH. <b><i>Methods:</i></b> The collagenase-induced ICH rat model was established. The neurological function of rats and the cerebral water content of rat brain tissue were measured to assess the brain injury. BV-2 cells were recruited and treated by LPS to mimic ICH-induced inflammatory response. qRT-PCR was used for the measurement of miR-340-5p. The protein levels of TNF-α, IL-6, and IL-1β were detected using ELISA. Luciferase reporter gene assay was performed to confirm the target gene. <b><i>Results:</i></b> Downregulation of miR-340-5p was detected in the serum of ICH patients and the brain tissues of ICH rats. Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), which were induced by ICH in vivo. In in vitro study, levels of TNF-α, IL-6, and IL-1β were significantly enhanced in cells after LPS treatment, but these increases were eliminated by overexpression of miR-340-5p. PDCD4 was a direct target gene of miR-340-5p. <b><i>Conclusion:</i></b> miR-340-5p protects against brain injury after ICH. miR-340-5p might exert an anti-inflammatory effect during the occurrence of ICH via targeting PDCD4.

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