Zhang Wei, Fan Chengcheng, Yi Zhongxue, Du Tao, Wang Nana, Tian Weizhu, Pan Qian, Ma Xiande, Wang Zhe
Fifth Department of Encephalopathy Rehabilitation, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Organization Department of the Party Committee, Department of Basic Sciences of Integrated Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Immunol Invest. 2024 Aug;53(6):872-890. doi: 10.1080/08820139.2024.2354268. Epub 2024 May 29.
Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases.
CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA.
TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro.
Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway.
脑缺血/再灌注损伤（CIRI）在全球范围内仍是一种死亡率很高的复杂疾病。跨膜蛋白79（TMEM79）在其他一些疾病中调节炎症和氧化应激。
使用C57BL/6J小鼠通过大脑中动脉闭塞-再灌注（MCAO/R）建立CIRI小鼠模型，对BV2细胞进行氧糖剥夺/复氧（OGD/R）以模拟CIRI。用携带慢病毒的TMEM79过表达载体转染或注射脑组织或BV2细胞。通过二氢乙锭（DHE）染色和氧化应激指标检测确定TMEM79对CIRI引发的氧化应激的影响。使用TUNEL染色和ELISA确定TMEM79在神经元凋亡和炎症中的调节作用。
TMEM79过表达减轻了MCAO/R诱导的神经功能缺损并减小了脑梗死范围。TMEM79可防止MCAO/R小鼠模型脑组织中的神经元死亡，并通过降低炎性细胞因子水平抑制炎症反应。此外，TMEM79显著减轻了OGD/R在BV2细胞中引起的炎症和氧化应激。TMEM79促进了Nrf2的激活并抑制了NLRP3和caspase-1的表达。挽救实验表明，Nrf2/NLRP3信号通路介导了TMEM79在体内和体外对CIRI的减轻作用。
总体而言，证实TMEM79通过调节Nrf2/NLRP3信号通路减轻CIRI。
