Salidroside protects against apoptosis-related mitochondrial dysfunction via activation of PI3K/AKT pathway in experimental traumatic brain injury

• Main Authors: Tsai, Hsinju, 蔡欣汝
• Other Authors: Chen, Szufu
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/95549009173254889464

碩士 === 國防醫學院 === 生理學研究所 === 99 === Traumatic brain injury (TBI) induces a complex sequence of apopotosis cascades that contribute to secondary tissue damage. Salidroside, a compound with a chemical structure of phenol glycosides as a strong antioxidant, has been shown to exert potent anti-inflammatory and anti-apoptotic properties in several in vitro studies. The aim of this study was to investigate whether salidrosde attenuated post-traumatic apoptosis-related mitochondrial dysfunction via modulating the PI3K/AKT-mediating signaling pathway. Male C57BL/6J mice were intraperitoneally injected with a single dose of salidroside (20mg/kg or 50mg/kg) or vehicle immediately after cortical impact injury. Both salidroside 20mg/kg and 50mg/kg improved functional outcomes including modified neurological severity score, rotarod, beam walking, and skill reaching test and reduced contusion volumes up to post-injury day 28. Salidroside 20mg/kg also attenuated brain edema and the number of degenerating neurons and apoptotic cells at 1 day as indicated by FJB and TUNEL staining. These changes were associated with a significant decrease of active caspase-3, Bax/Bcl-2 ratio, cytochrome c and Smac release to the cytosol. In addition to its protective action at the mitochondrial membrane, salidroside increased phosphorylation of AKT on Ser473 and Thr308. The beneficial effect of salidroside was abolished by preinjection of LY294002, a PI3K inhibitor. Moreover, LY294002 diminished the effect of SALD on phosphorylation of AKT and downstream targets, BAD and FOXO1. Our results suggest the beneficial effects of saliroside is mediated through activation of PI3K/AKT signaling pathways, which suppress the activation of caspase-3, mitochondrial dysfunction and apoptotic cell death, and thereby, lead to function recovery after TBI