神经保护肽[gly14]-humanin对脑外伤的保护作用及其机制研究-protective effect of neuroprotective peptide [ gly 14 ] - humanin on traumatic brain injury and its mechanism.docx

神经保护肽 神经保护肽[Gly14]-Humanin 对脑外伤的保护作用及其机制研究 英文摘要 PAGE PAGE III IV IV The Neuroprtective Effects and Mechanisms of [Gly14]-Humanin on Mice Traumatic Brain Injury Model Abstract Objective: Humanin (HN) has been identified as an endogenous peptide that inhibited AD-relevant neuronal cell death. [Gly14]-Humanin (HNG), a variant of HN in which the 14th amino acid serine was replaced with glycine, can reduce infarct volume and improve neurological deficits after ischemia/reperfusion injury. In this study, we aimed to exam the neuroprotective effect of HNG on traumatic brain injury (TBI) in mice and explored whether the protective effects were associated with regulating apoptosis and autophagy. Methods: Mice TBI model was established by weight drop device in adult mice based on procedures previously reported. Mice were pretreated with HNG (i.c.v., 0.1μg in 5 μL saline) or saline, and sacrificed at 48 h after TBI. Loss of plasmalemma integrity was evaluated by intraperitoneal injection of propidium iodide 1 h before sacrificing the animal. The number of PI-positive cells in injured cortex, dentate gyrus, CA1 and CA3 regions was counted. Furthermore, the cumulative loss of brain tissue was determined to explore whether PI-positive cells could represent TBI-induced cell lost. Moreover, motor test and Morris water maze were performed for detecting whether TBI-induced cell loss would result in behavior deficits. We examined whether pretreatment (i.c.v.) or posttreatment (i.p.) with HNG at different time can reduce brain tissue damage, and improve the recovery of motor and cognitive dysfunction. To explore the neuroprotective mechanism of HNG after TBI, mice was pretreated (i.c.v.) with HNG and brain tissues were obtained for specific protein analysis. We examined the levels of apoptosis and autophagy related proteins. Results: (1) Compared to vehicle-treated group, HNG pretreatment (i.c.v.) decreased the number of PI-positive cells in injured cortex, dentate gyrus, CA1 and 英文