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β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

羟基多巴胺 腹腔注射 内侧前脑束 自噬 氧化多巴胺 药理学 化学 内分泌学 左旋多巴 内科学 细胞凋亡 帕金森病 医学 纹状体 多巴胺 多巴胺能 生物化学 黑质 疾病
作者
Liping Huang,Minzhen Deng,Yu‐Ping He,Yongqi Fang
出处
期刊:Clinical and Experimental Pharmacology and Physiology [Wiley]
卷期号:42 (3): 269-277 被引量:21
标识
DOI:10.1111/1440-1681.12344
摘要

In this study, we investigated Beclin-1, light chain (LC)3B, and p62 expression in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats after β-asarone and levodopa (l-dopa) co-administration. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create the models, except in sham-operated rats. Rats were divided into eight groups: sham-operated group; 6-OHDA model group; madopar group (75 mg/kg, per os (p.o.)); l-dopa group (60 mg/kg, p.o.); β-asarone group (15 mg/kg, p.o.); β-asarone + l-dopa co-administered group (15 mg/kg + 60 mg/kg, p.o.); 3-methyladenine group (500 nmol, intraperitoneal injection); and rapamycin group (1 mg/kg, intraperitoneal injection). Then, Beclin-1, LC3B, and p62 expression in the mesencephalon were detected. The mesencephalon was also observed by transmission electron microscope. The results showed that Beclin-1 and LC3B expression decreased and that p62 expression increased significantly in the madopar, l-dopa, β-asarone, and co-administered groups when compared with the 6-OHDA model. Beclin-1 and LC3B expression in the β-asarone and co-administered groups were less than in the madopar or l-dopa groups, whereas p62 expression in the β-asarone and co-administered groups was higher than in the madopar or l-dopa groups. In addition, a significant decrease in autophagosome was exhibited in the β-asarone and co-administered groups when compared with the 6-OHDA group. Our findings indicate that Beclin-1 and LC3B expression decreased, whereas p62 expression increased after co-administration treatment. In sum, all data suggest that the co-administration of β-asarone and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity.
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