【摘要】 目的从病理、生化两方面研究天麻联苄化合物20C对帕金森病(parkinson’s disease, PD)小鼠模型的作用及机制。方法通过皮下注射丙磺舒、腹腔注射MPTP制备1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)联合丙磺舒(probenecid)模型,诱导PD小鼠模型;通过HE染色和免疫组化的方法评价组织病理改变;通过Western blot方法检测蛋白水平变化。结果病理生化结果显示,20C可以减少MPTP诱导的胃部硝基化α-突触核蛋白(nitrated-α-synuclein)。Western blot结果显示,20C可以降低MPTP诱导的肠道Toll样受体4(Toll-like receptors 4,TLR4)水平,降低磷酸化核转录因子(nuclear factor-κB,NF-κB)p65(p-p65)水平,降低白介素1β(interleukin-1β,IL-1β)水平,减轻炎症反应。结论 20C可以减少α-突触核蛋白聚集体和硝基化形式的生成,同时可以抑制TLR4-NF-κB p65通路,抑制p65的活化,减少IL-1β的生成,抑制炎症反应,对MPTP/p诱导的PD小鼠发挥保护作用。更多还原

【Abstract】 Objective To study the pathological and biochemical effect of bibenzyl compound 20 C on the mouse model of MPTP/p(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP/probenecid) and explore the mechanism. Methods A mouse model of MPTP/p was established. Mice received an intraperitoneal injection of MPTP and subcutaneous injection of probenecid. Pathological changes were examined by HE staining and immunohistochemistry while biochemical changes were detected by Western blot. Results Pathological and biochemical results showed that 20 C could reduce expressions of MPTP/p-induced nitrated-α-synuclein in the stomach. The results of Western blot suggested that 20 C reduced the level of Toll-like receptors 4(TLR4) in the MPTP/p model, decreased phosphorylated nuclear factor-κB(NF-κB) p65(p-p65), inhibited interleukin-1β(IL-1β) generation, and ameliorated inflammation. Conclusion 20 C can reduce the formation of α-synuclein aggregation and nitrated-α-synuclein, inhibit TLR4-NF-κB p65 pathway, prevent p65 from aetivation, decrease IL-1β, inhibit inflammation and protect mice from MPTP toxicity.更多还原