Yue Liu1, Hui Wang2, Ning Liu2, Juan Du2, Xiaobing Lan2, Xue Qi2, Chunlin Zhuang3, Tao Sun2, Yuxiang Li2, Jianqiang Yu4. 1. College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; College of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, PR China. 2. College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China. 3. College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; College of Pharmacy, the Second Military Medical University, Shanghai, 200433, PR China. 4. College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; Ningxia Hui Medicine Modern Engineering Research Center, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; Collaborative Innovation Center, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China. Electronic address: YujqLab@163.com.
Abstract
AIMS: In this study we aimed to explore the specific effect and mechanism of oxymatrine on neonatal rats hypoxic-ischemic brain damage. MATERIALS AND METHODS: Hypoxia-ischemia damage model was built by ligaturing the left common carotid artery in 7-day-old rat. Rat pups in OMT group received intraperitoneal injection with oxymatrine (120 mg/kg). Oxygen glucose deprivation/reperfusion model was created in hippocampal neurons. Neurological behavioral, histopathological alteration, cell viability, intracellular Ca2+ concentration, MMP and cell apoptosis were used in damage evaluation. KEY FINDINGS: The results shown that oxymatrine regulated brain damage and cell apoptosis by controlling NR2B-PI3K/Akt/GSK3β signaling pathway. SIGNIFICANCE: Neonatal hypoxic-ischemic brain damage is a destructive injury that leading to death and detrimental neurological deficits. Oxymatrine is a natural alkaloid compound that can alleviate the ischemic cerebral infarction. In the study, 120 mg/kg oxymatrine decreased neuroethology damage and neuronal damage in the cerebral cortex and the hippocampus CA3. Moreover, 0.2, 1, 5 μg/ml oxymatrine improved cell survival, decreased cell apoptosis. The utilization of LY293004 (PI3K signaling pathway inhibitor) also supported that oxymatrine ameliorated neonatal hypoxic-ischemic brain damage and cell injury by controlling NR2B-PI3K/Akt/GSK3β signaling pathway.
AIMS: In this study we aimed to explore the specific effect and mechanism of oxymatrine on neonatal ratshypoxic-ischemic brain damage. MATERIALS AND METHODS:Hypoxia-ischemia damage model was built by ligaturing the left common carotid artery in 7-day-old rat. Rat pups in OMT group received intraperitoneal injection with oxymatrine (120 mg/kg). Oxygen glucose deprivation/reperfusion model was created in hippocampal neurons. Neurological behavioral, histopathological alteration, cell viability, intracellular Ca2+ concentration, MMP and cell apoptosis were used in damage evaluation. KEY FINDINGS: The results shown that oxymatrine regulated brain damage and cell apoptosis by controlling NR2B-PI3K/Akt/GSK3β signaling pathway. SIGNIFICANCE: Neonatal hypoxic-ischemic brain damage is a destructive injury that leading to death and detrimental neurological deficits. Oxymatrine is a natural alkaloid compound that can alleviate the ischemic cerebral infarction. In the study, 120 mg/kg oxymatrinedecreased neuroethology damage and neuronal damage in the cerebral cortex and the hippocampus CA3. Moreover, 0.2, 1, 5 μg/ml oxymatrine improved cell survival, decreased cell apoptosis. The utilization of LY293004 (PI3K signaling pathway inhibitor) also supported that oxymatrine ameliorated neonatal hypoxic-ischemic brain damage and cell injury by controlling NR2B-PI3K/Akt/GSK3β signaling pathway.