Naringenin inhibits phosphorylated protein kinase C-δ and reduces inflammatory injury in rats after intracerebral hemorrhage

• Main Authors: XIAO Han, ZHANG Li, WANG Lu, CHEN Hui, GAN Hui, ZHENG Shuyue
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2020-05-01
• Series: Di-san junyi daxue xuebao
• Subjects: naringenin; intracerebral hemorrhage; protein kinase c-δ; inflammation
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/202001143.htm

Objective To investigate the effects of naringenin (NGN) on inflammatory injury after intracerebral hemorrhage (ICH) in rats and its possible molecular mechanism. Methods SD rats were randomly divided into sham group, ICH group, ICH+DMSO+PEG400 group, ICH+low-dose NGN group (10 mg/kg), ICH+middle-dose NGN group (20 mg/kg), ICH+high-dose NGN group (40 mg/kg), ICH+DMSO group, ICH+phorbol 12-myristate 13-acetate (PMA, PKC-δ activator) group, and ICH+PMA+NGN group. Autologous blood ICH model of SD rat was established, and the rats from the corresponding groups were intraperitoneally injected with NGN. In 24 h after ICH, the rats were evaluated for neurological function score, and then the rats were sacrificed to measure brain water content and perform HE staining for pathological changes. Western blotting was used to detect protein kinase C (PKC)-δ phosphorylation and expression of pro-inflammatory cytokines in sham group, ICH group, ICH+DMSO+PEG400 group, and ICH+ middle-dose NGN group. Intraventricular injection of PMA was carried out to induce PKC-δ phosphorylation in rats, and then ICH model was established, the expression of pro-inflammatory cytokines in rat brain tissues was detected by Western blotting. Results Compared with the ICH group and the solvent control group, NGN improved the neurological score (P < 0.05), reduced brain water content (P < 0.05), attenuated neuronal degeneration and cell death, and decreased PKC-δ phosphorylation and the expression levels of NF-κB, interleukin (IL)-1β, IL-6 after ICH (P < 0.01). PMA treatment resulted in the enhanced phosphorylation level of PKC-δ and the up-regulation of NF-κB, IL-1β, and IL-6 (P < 0.01) and reversed the effect of NGN on the decreased expression of NF-κB, IL -1β and IL-6 in rats after ICH (P < 0.01). Conclusion NGN attenuates the inflammatory injury after ICH in rats, which may be related to its inhibitory effect on PKC-δ phosphorylation.