摘要
To investigate the effects of 4-methyl-2-{[4-(toluene-4-sulfonyl)-thiomorpholine-3-carbonyl]-amino}-pentanoic acid isopropyl ester(HD5-6)against cerebral ischemia in rodents,the models with global and focal ischemia were induced by bilateral common carotid artery occlusion plus hypotension(BCAOH)and permanent cerebral artery occlusion(p-MCAO)in mice(n=10–12 per group in BCAOH;n=8 per group in p-MCAO)and rats(n=10-11 in each group).HD5-6 prolonged lifetime and improved neurological function.Neurological deficits score in HD5-6(30 mg/kg)decreased significantly.Malonaldehyde(MDA)in HD5-6-treated mice with ischemia considerably dropped.The infarction volume of the HD5-6-treated rats with MCAO-induced ischemia decreased significantly in the high dose group(P<0.05,i.g.and P<0.01,i.v.).Immunohistochemistry showed that Brain derived neurotrophic factor(BDNF)in the ipsilateral hemisphere increased and Vascular endothelial growth factor(VEGF)decreased with HD5-6 treatment.HD5-6 has protective effects against experimental cerebral ischemia in rodents and the action mechanism may involve anti-oxidation and neurogenesis.
基金
This work is supported by a grant from the national science and technology major project,a candidate drug for neurodegenerative diseases targeting FKBPs,(2009ZX09103-024).
