FK506 Potentiates NGF-induced Neurite Outgrowth After Hypxia In PC12 Cells And A Preliminary Study Of The Mechanisms

Peripheral nerve injury is a common orthopedic disabling disease. Peripheral nerve injury is often associated with neurological hypoxic-ischemic injury, especially after crush injury. Nerve regeneration process is actually damaged neurons form new axon growth or extend axons, and then with the target organ reconstruction of synaptic connections and restore its normal function in the process. Accelerate regeneration of axons after peripheral nerve injury,it is significant to improve the clinical effects after peripheral nerve injury and repair. Immunosuppressive drugs tacrolimus(FK506) has been found in the patient’s hand allograft promote nerve growth reflects the "deputy" effect, and has been shown to have neuroprotective and neurotrophic effects in experimental models in vitro and in vivo experiments, it can increase the extension of neurites and promote nerve regeneration rate. NGF has been recognized as having a neurotrophic and neuroprotective effects in nerve regeneration after nerve injury.By constructing a model of neuronal hypoxia, explored the drug to promote neurite growth and nerve growth factor synergy FK506, select the best drug concentration ratio.Further quantitative detection of the effects of different concentrations of FK506 in normoxic and hypoxic conditions, respectively PC12(neural cell research model) cell neurite outgrowth.FK506 detected in normoxic and hypoxic influence on PC12 cells HSP70(heat shock protein 70), HIF-1ɑ(hypoxia inducible factor) protein expression by immunoblotting(Western blotting), explore the FK506 protect neurons under hypoxia the possibility of damage mechanisms.The results show that no matter under normoxic and hypoxic condition, FK506 in 1-1000 nmol/L and NGF10 ng/ml can promote collaborative PC12 cell neurite outgrowth, which FK506 100 n M and NGF10ng/ml synergistic neurite outgrowth in PC12 cells after hypoxia of the most obvious;100n M FK506 and 10 ng / ml NGF can promote the expression of related protein,100nmol/L FK506 PC12 cells have protective effects of hypoxia, oxidative damage which may be related to the promotion of the role of HSP70, the expression of HIF-1ɑ concerned. The study has important clinical implications for the treatment of neurological damage after hypoxic injury.