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Suppressing inflammation by inhibiting the NF‐κB pathway contributes to the neuroprotective effect of angiotensin‐(1‐7) in rats with permanent cerebral ischaemia
Author(s) -
Jiang Teng,
Gao Li,
Guo Jun,
Lu Jie,
Wang Yao,
Zhang Yingdong
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.02105.x
Subject(s) - neuroprotection , oxidative stress , inflammation , pharmacology , receptor antagonist , antagonist , angiotensin ii , western blot , medicine , endocrinology , proinflammatory cytokine , receptor , chemistry , biochemistry , gene
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‐κB 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‐κB 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‐κB activity, which was accompanied by an up‐regulation of pro‐inflammatory cytokines and COX‐2. CONCLUSION AND IMPLICATIONS Our findings indicate that suppressing NF‐κB dependent pathway via Mas receptor may represent one mechanism that contributes to the anti‐inflammatory effects of Ang‐(1‐7) in rats with pMCAO.