ROCK2のダウンレギュレーションは、NF-κBシグナル伝達経路の抑制により、エタノール誘発脳神経障害を部分的に緩和します

Down-regulation of ROCK2 alleviates ethanol-induced cerebral nerve injury partly by the suppression of the NF-κB signaling pathway.

• Xinguo Li
• Jing Tong
• Jihui Liu
• Yibao Wang

抄録

Chronic alcohol consumption leads to hippocampal neuronal impairment, which related to neuronal death, oxidative stress, and inflammatory response. Rho-associated protein kinase 2 (ROCK2) is a major regulator in the central nervous system injury. However, the effects of ROCK2 in ethanol-induced brain injury have not been explored. In this work, we investigated the neuroprotective effects and the mechanism of ROCK2 inhibition . Wistar rats were exposed to 37% ethanol for 8 weeks to establish brain injury models. Morris water maze test was performed to evaluate cognitive function, and we found that the down-regulation of ROCK2 reduced the escape latency and increased the passing times and percentage of time spent in the target quadrant of rats. The results of H&E staining and Nissl staining showed that ROCK2 inhibition alleviated the pathological injury induced by ethanol. PI staining and Western blot confirmed that inhibiting ROCK2 attenuated the neuronal death and apoptosis as reflected by the reduced PI-positive neurons and the decreased expression of cleaved-caspase-3 and cleaved-caspase-9. Furthermore, the down-regulation of ROCK2 ameliorated the oxidative stress and inflammatory response induced by ethanol in rats as reflected by the up-regulation of IL-10, SOD, and GSH and reduction of TNF-α, IL-6, and MDA respectively. Additionally, Western blot and EMSA analysis revealed that the down-regulation of ROCK2 suppressed the nuclear transfer of NF-κB p65. In conclusion, our data suggested that ROCK2 inhibition ameliorated ethanol-mediated hippocampal neuronal impairment by anti-apoptotic, anti-inflammatory, anti-oxidative effects at least partially through the suppression of the NF-κB pathway.