The Mechanism Of GDNF/TNF-α Induced Neuroprotection By Hypoxia Preconditioning In Rats

Objective:To detect the expression GDNF / TNF-α in the brain of rat after hypoxic preconditioning;to investigate the neuroprotective effect of GDNF and TNF-α on hypoxic preconditioned ischemic and its mechanism.Methods:Seventy male SD-rats were randomly divided into eight groups, control group(N, n=5), sham-operated group(S, n=12), the operated of middle cerebral artery occlusion group(M, n=12), hypoxia-preconditioned group(H, n=5), hypoxia-preconditioned and middle cerebral artery occlusion group(HM, n=12), hypoxia-preconditioned and middle cerebral artery occlusion and Inhibitors group(HMI, n=12), hypoxia-preconditioned and middle cerebral artery occlusion and normal saline group(HMN, n=12). We evaluated the neurological function of rats 24 h after middle cerebral artery occlusion according to Longa5 criteria and infart volume using Image J software. Real-time PCR was applied to detecte the expression leves of GDNF and TNF-α,and TNF-α protein was also verified using western blotting.Results:Compared with the operated of middle cerebral artery occlusion group, the neurological impairment of hypoxia-preconditioned and middle cerebral artery occlusion group was alleviated(P < 0.05), and its infarct volume was reduced significantly from 22.35±2.87% to 15.40±3.10%(P<0.05). Compared with HM, the neurological impairment of HMI was increased significantly(P<0.05),the infract volume of HMI was reduced(P<0.05).Compared with N,the expression levels of GDNF gene of H and M groups was up-regulated(P<0.05),while the expression levels of TNF-α gene and its protein were reduced significantly(P<0.05), the changes in H was significantly. Compared with M, the expression levels of GDNF gene of HM was up-regulated(P<0.05),while the expression levels of TNF-α ene and its protein were reduced significantly(P < 0.05).Compared with HM,he expression levels of GDNF gene of HMI was reduced significantly(P<0.05),while the expression levels of TNF-α gene was up-regulated(P<0.05).Conclusions Hypoxia preconditioning can alleviate the neurological impairment and reduced the infarct volume, which also reduce the damage of neurons. The expression levels of GDNF gene is increased significantly, while the expression levels of TNF-α gene and protein are decreased significantly. This suggest that GDNF and TNF- α might involved in the neuroprotection induced by hypoxia precondition.