期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 167, 期 7, 页码 1520-1532出版社
WILEY
DOI: 10.1111/j.1476-5381.2012.02105.x
关键词
stroke; inflammation; Ang-(1-7); A-779; NF-kappa B
资金
- Natural Science Foundation of Jiangsu Province [BK2010116]
- Medical Science and Technology Foundation for Young Scientists of Nanjing City [QYK09186]
BACKGROUND AND PURPOSE Angiotensin-(1-7) [Ang-(1-7)] has anti-inflammatory effects in peripheral organs, but its effects in ischaemic stroke are unclear as yet. We investigated whether its anti-inflammatory effect contributes to the neuroprotection induced by Ang-(1-7) in a rat model of permanent middle cerebral artery occlusion (pMCAO). EXPERIMENTAL APPROACH We infused Ang-(1-7), Mas receptor antagonist A-779, angiotensin II type 2 receptor antagonist PD123319 or artificial CSF into the right lateral ventricle of male Sprague-Dawley rats from 48 h before onset of pMCAO until the rats were killed. Twenty-four hours after pMCAO, the neuroprotective effect of Ang-(1-7) was analysed by evaluating infarct volume and neurological deficits. The levels of oxidative stress were detected by spectrophotometric assay. The activation of NF-kappa B was assessed by Western blot and immunohistochemistry analysis. The level of COX-2 was tested by Western blot analysis and concentrations of pro-inflammatory cytokines were measured by elisa. KEY RESULTS Infusion of Ang-(1-7), i.c.v., significantly reduced infarct volume and improved neurological deficits. It decreased the levels of oxidative stress and suppressed NF-kappa B activity, which was accompanied by a reduction of pro-inflammatory cytokines and COX-2 in the peri-infarct regions. These effects of Ang-(1-7) were reversed by A-779 but not by PD123319. Additionally, infusion of A-779 alone increased oxidative stress levels and enhanced NF-kappa B activity, which was accompanied by an up-regulation of pro-inflammatory cytokines and COX-2. CONCLUSION AND IMPLICATIONS Our findings indicate that suppressing NF-kappa B dependent pathway via Mas receptor may represent one mechanism that contributes to the anti-inflammatory effects of Ang-(1-7) in rats with pMCAO.
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