ABSTRACT
Objective To investigate the protective effect and mechanism of angiotensin-(1-7) on cerebral ischemia-reperfusion injury in rats.Methods A rat model of middle cerebral artery occlusion (MCAO) reperfusion was established by non-invasive arteriolar clamping of bilateral common carotid artery in SD rats.The sham operation group and the model group were given artificial cerebrospinal fluid,and the low,medium and high dose treatment groups were given Ang-(1-7),with a dose of 1 pmol/0.5 μl/h,100 pmol/0.5 μl/h and 10 nmol/0.5 μl/h,respectively.After 24 h of arterial occlusion and reperfusion,Garcia JH standard was used to evaluate the neurological function of rats.The water content of brain tissue was determined by gravimetric method.The volume of cerebral infarction was determined by TIC staining method.The expression of Toll-like receptors 4 (TLR4) and nuclear factor-κB (NF-κB)p65 protein in ischemic parietal cortex were determined by Western Blot.The content of serum intercellular cell adhesion molecule-1(ICAM-1) and tumor necrosis factor-α (TNF-α) were detected by ELISA.Results Compared with the model group,the low,medium and high Ang-(1-7) dose groups significantly improved the neurological function scores of MACO rats (all P＜0.05).Compared with the model group,the brain water content of the high-dose Ang-(1-7) treatment group was significantly decreased (P＜0.05).Compared with the model group,the cerebral infarction volume of the rats in the low,medium and high Ang-(1-7) dose groups was significantly reduced (all P＜0.05).Compared.with the model group,the expression of TLR4 and NF-κB p65 protein in the middle and high-dose Ang-(1-7) treatment group was decreased (all P＜0.05),and the levels of ICAM-1 and TNF-α in serum was decreased (all P＜0.05).Conclusions Ang-(1-7) has a protective effect on cerebral ischemia-reperfusion injury of MACO rats,and its mechanism may be related with the inhibition of TLR4/NF-κB pathway.