The Mechanism Of Shh Signal Pathway Induced Neuroprotection By Hypoxia Preconditioning In Rats

Objective To study the molecular mechanisms of Shh signal pathway induced neuroprotection in hypoxia preconditioning in ischemic SD rats, and to discuss the relationship between molecular of HIF-1α, Shh signal pathway and Ang-1 in ischemic injury.Methods Seventy SD rats were randomly divided into seven groups, control group(Normal, N, n=10), sham-operated group(Sham operation, S, n=10), the operated group(Middle cerebral artery occlusion, M, n=10), hypoxia-preconditioned group(Hypoxic preconditioning, H, n=10), hypoxia-preconditioned and operated group(Hypoxic preconditioning and Middle cerebral artery occlusion, HM, n=10), lateral ventricle control group(Hypoxic preconditioning, Middle cerebral artery occlusion and Normal, HMN, n=10) and inhibitor group(Hypoxic preconditioning,Middle cerebral artery occlusion and inhibitor, HMI, n=10). We assessed the animal models by Longa’ 5 points neurological deficit score, after 24 hours’ surgery; through measured infarct size with TTC. Quantitative Reverse Transcript-PCR assay was applied to detect the expression levels of HIF-1α and Gli-1,and western blot was used to verify the target protein of Gli-1 and Ang-1.Results1. Neurological scores: group HM comparison with group M, neurological dysfunction was significantly reduced(P<0.05), group HMI comparison with group HMN, neurological dysfunction significantly aggravated(P<0.05).2. Area of cerebral infarct: group HM comparison with group M, infarct area was significantly reduced(P<0.05), group HMI comparison with group HMN, infarct area was significantly increased(P<0.05).3. Group M comparison with group N and group S, HIF-1α m RNA expression was significantly increased(P<0.05); group HMN comparison with group HMI, HIF-1α m RNA expression was significantly increased(P<0.05). Group M comparison with group N and group S, Gli-1 m RNA expression was significantly increased(P<0.05).4. Group M comparison with group N and group S, Gli-1 protein expression was significantly increased(P<0.05); group HM comparison with group M, Gli-1 protein expression was significantly increased(P<0.05). Group HM comparison with group M, Ang-1 protein expression was significantly increased(P<0.05); group HMI comparison with group HMN, Ang-1 protein expression was significantly lower(P<0.05).Conclusions Hypoxic preconditioning can reduce infarction size, improve cerebral ischemic symptom and has an important protective role of the neurovascular unit by endogenous protective mechanism; hypoxic preconditioning may improve expression levels of Ang-1 by upregulating Shh signaling pathway, resulting in the protective effects of neurovascular; there may be no relationship between HIF-1α and Shh signaling pathway upregulation after hypoxic preconditioning, but it depends on further study.