摘要
目的探讨血管紧张素-（1-7）[Ang-（1-7）1对大鼠脑缺血再灌注损伤后核因子-κB（NF-κB）及其下游炎症因子的调控作用。方法将42只SD大鼠按随机数字表法分为假手术组、缺血组及Ang-（1-7）治疗组，每组各14只。缺血组及Ang-（1-7）治疗组均行大脑中动脉栓塞术（MCAO）。用微型渗透泵分别给予假手术组及缺血组人工脑脊液（aCSF）0．5μL／h治疗，给予Ang-（1-7）治疗组Ang-（1-7）（100pmol／L，0．5μL／h）治疗。脑缺血再灌注损伤后24h用Western blotting法检测各组大鼠缺血侧皮层细胞核内NF-κBp65蛋白的表达，免疫组化染色检测NF-κBp65的空间分布以及阳性细胞数，酶联免疫吸附测定（ELISA）法测定血清肿瘤坏死因子-α（TNF-α、白介素-1β（IL-1β）含量。结果Ang-（1-7）治疗组缺血侧顶叶皮层细胞核内NF-κBp65蛋白较缺血组降低约46％，差异有统计学意义（P〈0．05）。Ang-（1-7）治疗组缺血侧皮层细胞NF-κBp65由胞浆向胞核的移位被显著抑制，NF-κBp65阳性表达率较缺血组降低约29％，差异有统计学意义（P〈0．05）。Ang-（1-7）治疗组缺血侧皮层炎症因子TNF-α、IL-1β的表达[（71.603±18．539）pg／mL、（44．648±10．387）pg／mL]较缺血组[（104．763±24．412）pg／mL、（64．787±14．441）pg／mL]均有所降低，差异有统计学意义（P〈0．05）。结论Ang-（1-7）能显著减轻脑缺血再灌注损伤中的炎症反应，其可能通过作用于Mas受体或拮抗血管紧张素Ⅱ的促炎作用，进而减轻氧化应激反应而实现。
Objective To investigate the regulative effect of exogenous Angiotensin-（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, 0.5μL/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-histoehemical assay. The concentrations of tumor necrosis factor-α （TNF-α） and intedeukin-1β （IL-1β） in serum were detected by ELISA. Results A significantreduction 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-I[3 （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 orAng-（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.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2013年第1期19-23,共5页
Chinese Journal of Neuromedicine
基金
江苏省科技厅自然科学基金（BK2010116）
