MicroRNA-21 and microRNA-146a negatively regulate the secondary inflammatory response of microglia after intracerebral hemorrhage

摘要

Background: A secondary inflammatory response is the most important mechanism of injury after intracerebral hemorrhage (ICH). Previous studies found microRNAs (miRs) expressed abnormally in the perihematomal tissue and blood of patients with ICH and demonstrated that miRs were related to pathophysiological changes and prognosis after ICH, and the development of inflammation. Methods: We induced a microglial inflammatory response by lipopolysaccharide (LPS) to construct a microglial inflammatory model. MiR-21/miR-146a overexpression adenovirus was used to infect microglia to increase miR-21/miR-146a expression. MiR-21, miR-146a, IRAK1, MMP-9, TNF-α, TIMP3 and other inflammatory factors were analyzed. Then, miR-21/miR-146a overexpression adenovirus was injected into rats with ICH to modulate the expression. Inflammation, brain edema, and neurological scores were assessed. Results: For in vitro and vivo experiments, overexpression of miR-21/miR-146a decreased the expression of IL-1β, IL-6, IL-8, IRAK1, MMP-9 and TNF-α, meanwhile increased the expression of TIMP3 significantly (P<0.001), compared with the negative control group. Additionally, miR-21 and miR-146a reduced brain edema and improved the neurological function in ICH rats. Conclusion: Our study proved that miR-21 and miR-146a could negatively regulate the inflammatory response of microglia after ICH and provided a new theoretical basis for the treatment of secondary inflammatory injury after ICH in humans.