Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice

Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-l,2,3,6 tetrahydropyridine （MPTP）-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson＇s disease. Oral administration of octacosanol （100 mg/kg） significantly improved behavioral impairments Jn mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signa transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson＇s disease.

28醇对MPTP致帕金森病模型小鼠行为学的作用及其机制

目的观察28醇对帕金森病模型小鼠行为学改善作用,并探讨其可能的机制。方法 75只成年雄性C57小鼠随机分为5组:对照组,模型组,28醇低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高剂量组(100 mg/kg),每组15只。除对照组外,其他各组间隔2 h腹腔注射MPTP 16 mg/kg共4次造模。28醇各剂量组按剂量连续灌胃给药2周,其他组给予等量0.5%缩甲基纤维素钠(CMC)无菌水。行为学检测采用转杆试验和自发运动试验,Nissl染色组化实验检测纹状体神经元数量及状态,Western blot实验检测黑质区p-Erk1/2、p-p38 MAPK、p-JNK表达。结果与对照组相比,28醇高剂量组转杆试验和自发运动试验成绩改善(P<0.05)。28醇中剂量和高剂量组含有Nissl小体的神经元显著增多并染色加深(P<0.05),黑质区p-p38 MAPK、p-JNK蛋白表达与模型组相比下降(P<0.05),p-Erk1/2表达与模型组无显著性差异。结论 28醇可改善帕金森病小鼠行为学指标。可能通过调节MAPKs家族信号转导因子p-p38 MAPK、p-JNK蛋白表达,减少黑质纹状体通路的损伤发挥其作用。

促红细胞生成素改善实验性变态反应性脑脊髓炎症状观察

目的：观察促红细胞生成素（EPO）对实验性变态反应性脑脊髓炎（EAE）的神经保护作用。方法：制备EAE小鼠模型,对EPO干预组和EAE对照组小鼠进行临床症状及病理组织学评估;提取制备外周及中枢浸润淋巴细胞,应用流式细胞仪观察CD4＋T亚群、炎性细胞因子水平以及细胞死亡情况;应用LDH测定评估不同浓度EPO对外周淋巴细胞死亡的影响。结果：EPO可改善EAE小鼠临床症状和病灶局部淋巴细胞浸润（P〈0.05）;EPO干预组小鼠中枢浸润细胞以及外周淋巴细胞CD4＋T细胞比例下降,IL-17和IFN-γ等炎性因子水平降低（P〈0.05）,而细胞死亡比例以及IL-10、CD4＋CD25＋调节性T细胞水平与EAE对照组无显著差异（P〉0.05）;1~1 000 U/ml浓度范围内EPO对外周单核淋巴细胞LDH的释放无显著影响（P〉0.05）。结论：EPO可以通过减少病灶炎性细胞浸润以及抑制IL-17和（或）IFN-γ水平等途径,对EAE具有神经保护作用。