Effects of huwentoxin on tumor necrosis factor apoptotic pathway in the hippocampus of a rat model of cerebral ischemia / 中国组织工程研究

ABSTRACT

BACKGROUND:Ion channel analytical technique has verified that huwentoxin is an N-type Ca2+channel blocker affecting on presynaptic membrane. OBJECTIVE:To observe the effects of N-type Ca2+channel blocker huwentoxin on expressions of tumor necrosis factorα, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 in the hippocampi of rat models of global cerebral ischemia reperfusion injury. METHODS:Rat models of global cerebral ischemia and subarachnoid catheter were established using Pulsinel i 4-vessel occlusion and then received infusion of huwentoxin or normal saline via a PE10 tube. Morphological changes in the mitochondria and ultrastructure of pyramidal neurons in the hippocampal CA1 region of rats with global cerebral ischemia reperfusion injury were observed using electron microscope. The expressions of tumor necrosis factorα, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 were measured using RT-PCR. RESULTS AND CONCLUSION:Huwentoxin could maintain the basic morphology of mitochondria of rats with global cerebral ischemia reperfusion injury and decrease the expressions of tumor necrosis factorα, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 mRNA. Results suggested that huwentoxin as a novel N-type Ca2+channel blocker could block extracellular Ca2+influx, reduce intracellular Ca2+concentration, diminish a series of pathological lesion induced by intracellular Ca2+overload, protect nerve cells, and lessen the injury to nerve cells of hippocampus after ischemia and hypoxia.