关键词: 肝细胞生长因子, 皮质神经元, 缺氧/复氧, 细胞凋亡, PI3K/Akt, Caspase-3

Abstract: Objective To investigate the protective effect of hepatocyte growth factor (HGF) on cultured Sprague-Dawley rat cortical neurons injured by hypoxia/reoxygenation. Methods Primary cultured cerebral cortical neurons were isolated from newborn rats. Neurons were pre-incubated with different concentrations (15, 30 and 60 μg/L) of HGF, and then treated with oxygen deprivation for 6 h/normoxic condition for 12 h. The cell viability was detected by MTT. Apoptosis were measured by Hoechst 33258 staining and Flow Cytometer. Lactate dehydrogenase (LDH) and caspase-3 activity were determined by colorimetry. Results Compared with normal group, hypoxia/reoxygenation treatment significantly decreased the cell viability, increased LDH activity and the percentage of apoptotic cells. Pretreatment of HGF for 12 h could remarkably reverse the decrease of cell viability and the increase of apoptosis rate in neurons induced by hypoxia/reoxygenation treatment. HGF pre-treatment also attenuated the activity of LDH and caspase-3 in a dose-dependent manner. The effects of HGF could be inhibited by a special PI3K/Akt pathway inhibitor, LY294002. Conclusions HGF could at-tenuate rat cortical neuron injury induced by hypoxia/reoxygenation. The neuroprotective effect of HGF may be related to activating PI3K/Akt pathway, and further suppressing the expression of caspase-3.

Key words: hepatocyte growth factor, cortical neurons, hypoxia/reoxygenation, Apoptosis, PI3K/Akt, Caspase-3