Modulation of anginotensin-(1-7) on nuclear factor-κB and its downstream proinflammatory cytokines in rats after cerebral ischemic-reperfusion injuries
10.3760/cma.j.issn.1671-8925.2013.01.005
- VernacularTitle:血管紧张素-(1-7)对大鼠脑缺血再灌注损伤后核因子-κB及下游炎症因子的调控作用
- Author:
Teng JIANG
1
;
Li GAO
;
Jie LU
;
Jian-Ying ZHANG
;
Ying-Dong ZHANG
Author Information
1. 南京医科大学附属南京第一医院神经内科
- Keywords:
Angiotensin-(1-7);
Cerebral ischemia reperfusion;
Nuclear factor-κB;
Inflammatory cytokine
- From:
Chinese Journal of Neuromedicine
2013;12(1):19-23
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the regulative effect of exogenous Angiotcnsin-(1-7) [Ang(1-7)] on nuclear factor-κB (NF-κB) and its downstream proinflammatory cytokines in rats after cerebral ischemic-reperfusion injuries.Methods Forty-two male SD rats were randomly divided into sham-operated group,control group and Ang-(1-7) treatment group (n=14); cerebral ischemia in control group and Ang-(1-7) treatment group was induced by transient middle cerebral artery occlusion (MCAO).The rats in the sham-operated group and control group were infused with artificial cerebrospinal fluid (aCSF,0.5 μL/h) while rats in the Ang-(1-7) treatment group were with Ang-(1-7)(100 pmol,0.5 μL/h)into the lateral ventricle by implanted osmotic minipumps following reperfusion.At 24 h after reperfusion,all rats were sacrificed to detect the expression of NF-κB p65 subunits in cell nuclei of the ischemic cortex by Western blotting.The spatial distribution of NF-κB p65 subunits in ischemic cerebral tissues was detected by immuno-histochemical assay.The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by ELISA.Results A significant reduction of NF-κB p65 expression in cell nuclei by 46％ in the Ang-(1-7) treatment group was noted as compared with that in control group (P＜0.05).The nuclear translocation of NF-κB p65 in the ischemic cortical cells in the Ang-(1-7) treatment group was significantly reduced,and the rate of NF-κB p65 positive cells was decreased by 29％ as compared with that in control group (P＜0.05).Besides,the serum levels of TNF-α (71.603±18.539 pg/mL) and IL-1 β (44.648±10.387 pg/mL) in the Ang-(1-7) treatment group were obviously decreased as compared with those in the control group (104.763±24.412 pg/mL,64.787±14.441 pg/mL,P＜0.05).Conclusion Exogenous administration of Ang-(1-7) could attenuate inflammatory reaction following cerebral ischemia,perhaps by interacting with Mas receptor or through the antagonism against the pro-inflammatory effect of Ang Ⅱ.
