Baocheng Zhang1, Mingqiang Gao2, Jie Shen3, Daikun He1. 1. Department of ICU, Jinshan Hospital afflitated to Fudan university, Shanghai, China. 2. Department of Emergency, Jinshan Hospital afflitated to Fudan university, Shanghai, China. 3. Department of ICU, Jinshan Hospital afflitated to Fudan university, Shanghai, China. Electronic address: jieshenicu@sina.com.
Abstract
BACKGROUND AND AIMS: Cerebral ischemia and reperfusion (I/R) could produce excess reactive oxygen species (ROS), which in turn induce neurological dysfunction and inflammation in cerebral tissues. This study was designed to study the effect of methane on cerebral I/R injury. METHODS: Fifty Sprague-Dawley (SD) rats were used to induce an animal model of cerebral I/R injury. Methane was mixed with air to achieve a final concentration of 2.2%. Rats started to inhale methane-air mixture after ischemia and continued it during the reperfusion. The neurological deficits, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the brain tissue were examined. The protein kinase B (Akt) phosphorylation and heme oxygenase-1 (HO-1) expression was measured by Western Blot. The neurological deficits were re-measured after rats were treated with the HO-1 inhibitor Zinc protoporphyrin IX (ZnPP-IX), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine. RESULTS: Cerebral I/R induced neurological deficit, which was significantly decreased by methane. MDA and TNF-α levels were significantly enhanced by cerebral I/R, while methane caused significant reduction of MDA and TNF-α levels. Methane significantly increased Akt phosphorylation and HO-1 expression. The HO-1 inhibitor ZnPP-IX, PI3K inhibitor LY294002 and Akt inhibitor triciribine all significantly abolished the effect of methane on neurological deficit. CONCLUSIONS: This finding suggests the possible application of methane for cerebral I/R injury and PI3K/Akt/HO-1 dependent antioxidant pathway may be involved.
BACKGROUND AND AIMS: Cerebral ischemia and reperfusion (I/R) could produce excess reactive oxygen species (ROS), which in turn induce neurological dysfunction and inflammation in cerebral tissues. This study was designed to study the effect of methane on cerebral I/R injury. METHODS: Fifty Sprague-Dawley (SD) rats were used to induce an animal model of cerebral I/R injury. Methane was mixed with air to achieve a final concentration of 2.2%. Rats started to inhale methane-air mixture after ischemia and continued it during the reperfusion. The neurological deficits, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the brain tissue were examined. The protein kinase B (Akt) phosphorylation and heme oxygenase-1 (HO-1) expression was measured by Western Blot. The neurological deficits were re-measured after rats were treated with the HO-1 inhibitor Zinc protoporphyrin IX (ZnPP-IX), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine. RESULTS: Cerebral I/R induced neurological deficit, which was significantly decreased by methane. MDA and TNF-α levels were significantly enhanced by cerebral I/R, while methane caused significant reduction of MDA and TNF-α levels. Methane significantly increased Akt phosphorylation and HO-1 expression. The HO-1 inhibitor ZnPP-IX, PI3K inhibitor LY294002 and Akt inhibitor triciribine all significantly abolished the effect of methane on neurological deficit. CONCLUSIONS: This finding suggests the possible application of methane for cerebral I/R injury and PI3K/Akt/HO-1 dependent antioxidant pathway may be involved.