Overexpression of miR-146a inhibits the apoptosis of hippocampal neurons of rats with cerebral hemorrhage by regulating autophagy

Abstract

In this study, to investigate the effect of overexpression of miR-146a on autophagy of hippocampal neurons in rats with intracerebral hemorrhage (ICH), 72 Sprague-Dawley rats were randomly divided into the sham, ICH, miR-146a agomir, and miR-146a agomir control groups. The ICH model was constructed by injection of collagenase VII. The apoptosis of hippocampal neurons was measured by TUNEL assay. The levels of LC3 and Beclin 1 were analyzed by immunohistochemistry. Mitochondrial autophagy was examined by transmission electron microscopy. The levels of LC3A, LC3B, Beclin 1, Bax, Bcl-2, and cleaved caspase 3 were examined by Western blot. Western blot was also used to evaluate the expression of nuclear factor κB signaling pathway-related factors. To examine the effect of autophagy inhibitor (3-methyladenine (3-MA)) on miR-146a-regulated apoptotic protein expression, 30 rats were further divided into the sham, ICH, miR-146a agomir, 3-MA, and miR-146a + 3-MA groups. The levels of Bax, Bcl-2, and cleaved caspase 3 were examined by Western blot. Compared with the sham group, the nerve function scores, brain water content, the percentage of apoptotic cells, and the expression levels of LC3, Beclin 1, Bax, cleaved caspase 3, and p-P65 in the hippocampus of rats in the ICH group were all significantly increased ( p < 0.05), whereas the expression levels of miR-146a, Bcl-2, and p-IκBα were markedly decreased ( p < 0.05). Mitochondrial autophagy was also evident. Furthermore, compared with the ICH group, the results of the abovementioned tests in the miR-146a agomir group were reversed. The overexpression of miR-146a inhibited the autophagy of hippocampal neurons in rats with ICH.

BMAL1 attenuates intracerebral hemorrhage-induced secondary brain injury in rats by regulating the Nrf2 signaling pathway

“…Although the regions of hippocampus and cortex are not in situ hemorrhagic foci, ICH can lead to secondary nerve injury, including neuronal death and apoptosis in the hippocampus and cortex (5,34). In the present study, ICH rats exhibited cognitive decline, and the hippocampus and cortex presented neuronal death and apoptosis-related changes, consistent with previous studies (35,36). The mechanisms of brain injury after ICH include not only the initial mechanical injury induced by the hematoma mass effect, but also subsequent damage called SBI (1).…”

Mesenchymal Stem Cell Exosomal miR-146a Mediates the Regulation of the TLR4/MyD88/NF-κB Signaling Pathway in Inflammation due to Diabetic Retinopathy

“…miR-146a is a single-stranded noncoding small RNA that regulates gene expression by binding to target mRNAs. As an important innate immune signal regulator, miR-146a is involved in the immune response process of various autoimmune and infectious diseases [ 14 ]. Exosomes are nanoscale particles that can effectively deliver miRNA to recipient cells.…”

MiR-146a alleviates acute lung injury via inhibiting Notch 1 signaling pathway targeting macrophage

“…The result further indicated that miR-146a overexpression corrected inflammation and edema in ALI mice. Evidences exhibit that overexpression of miR-146a inhibits the apoptosis in rat hippocampal neurons [27] and in primary human retinal microvascular endothelial cells [28]. However, few studies suggested miR-146a induced apoptosis in neuroblastoma cells and inhibited proliferation [29] and induced apoptosis in osteoblast [30][31][32][33].…”