灯盏乙素对痴呆大鼠脑组织神经炎性反应的干预作用

Intervention of Scutellarin on Neuro-inflammatory Reaction in the Brains of Rats with Dementia

目的:观察灯盏乙素对痴呆模型大鼠脑组织中几种炎性因子表达的影响,探讨其可能的抗炎治疗机制。方法:Wistar大鼠42只,随机分为5组,正常对照组、假手术组、学习记忆损伤模型组、灯盏乙素处理组和脑复康处理组。用双侧脑室注射β淀粉样蛋白(Aβ25-35)联合ip D-半乳糖方法建立痴呆大鼠模型;造模后次日分别用28 mg.kg-1灯盏乙素和365 mg.kg-1脑复康连续ig 20 d;实时定量聚合酶链法(RT-PCR)测定大鼠脑组织核因子(nuclear factor,NF)-κB p65表达的变化;免疫组织化学方法检测大鼠脑组织白介素-1β(IL-1β),白介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)的表达。结果:与正常组和假手术组相比,模型组大鼠脑组织中NF-κB p65 mRNA表达水平上升了27%和31%(P<0.05),IL-1β,IL-6,TNF-α表达的阳性细胞分值正常组(1.3±0.5,1.6±0.5,1.6±0.69)和假手术组(1.5±0.5,1.6±0.7,2.0±0.7)。模型组明显上升(2.9±0.7,3.2±0.8,3.0±0.82),P<0.05。灯盏乙素处理后NF-κB p65的mRNA表达水平下调了20%(P<0.05),IL-1β,IL-6和TNF-α表达的阳性细胞分值明显下降(2.1±0.67,2.3±0.70,2.2±0.53),P<0.05。结论:灯盏乙素可阻断痴呆大鼠脑组织中NF-κB p65的活化,抑制炎性因子释放,改善学习记忆能力,通过减轻神经炎症损伤起到神经保护的作用。

Objective： To observe the effect of scutellarin（Scu） on expression of several inflammatory factors in the brains of rats with dementia and to reveal the possible therapeutic mechanism on dementia.Method： Wistar rats were randomly divided into 5 groups,ie,normal,sham operation,learning and memory deficit model,Scu treatment and piracetam treatment groups.The rat dementia model was produced by bilateral ventricle injection with β-amyloid peptide（Aβ25-35） and abdominal cavity injection with D-galactose.The rats in Scu or piracetam group were treated with 28 mg.kg-1 and 365 mg.kg-1 of 0.5% Scu or 64 g.L-1 piracetam by intragastric gavage（ig） for 20 days after modeling.NF-κB p65 at mRNA levels were detected by real-time PCR,and the expressions of interleukin-1β（IL-1β）,interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were observed by immunohistochemistry method in the brain of rats.Result： As compared to normal or sham operation groups,NFκB p65 mRNA expression in the model group was up-regulated by 27% and 31%,the expressions of IL-1β,IL-6 and TNF-α were increased from 1.3 ± 0.48,1.6 ± 0.52,1.6 ± 0.69 and 1.5 ± 0.53,1.6 ± 0.70,2.0 ± 0.67 to 2.9 ± 0.74,3.2 ± 0.79,3.0 ± 0.82（P 0.05）.After treatment by Scu,NF-κB p65 mRNA expression were down-regulated by 20%（P 0.05） and scores of positive cells of IL-1β,IL-6 and TNF-α were respectively decreased by 2.1 ± 0.67,2.3 ± 0.70,2.2 ± 0.53（P 0.05） in brain tissues as compared to learning and memory deficit group.Conclusion： By preventing activation of NF-κB p65 and inhibiting releasing of mediators of inflammation,Scu may be able to improve the ability of learning and memory of the rats with dementia and to educe neuroprotective effects.