Ultrasound-triggered effects of the microbubbles coupled to GDNF- and Nurr1-loaded PEGylated liposomes in a rat model of Parkinson's disease.
Ultrasound-triggered effects of the microbubbles coupled to GDNF- and Nurr1-loaded PEGylated liposomes in a rat model of Parkinson's disease.
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在帕金森病大鼠模型中，微泡与负载 GDNF 和 Nurr1 的聚乙二醇化脂质体偶联的超声触发效应。
DOI：
10.1002/jcb.26608
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Junfang Teng
中科院分区：
文献类型：
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作者：
Peijian Yue;Lin Gao;Xuejing Wang;Xuebing Ding;Junfang Teng
本研究的目的是研究超声触发胶质细胞源性神经营养因子（GDNF）+核受体相关因子1（Nurr 1）-聚乙二醇（PEG）化脂质体偶联微泡（PLs-GDNF + Nurr 1-MBs）对帕金森病（PD）大鼠模型中行为障碍和神经元丢失的影响。对未负载的PEG化脂质体偶联微泡（PLs-MB）进行了ζ电位、粒度和浓度表征。采用6-羟基多巴胺（6-OHDA）建立PD大鼠模型。采用旋转、爬杆和悬吊试验检测行为障碍。采用免疫组织化学染色法检测神经元酪氨酸羟化酶（TH）和多巴胺转运蛋白（DAT）的表达。Western blot和定量真实的-时间PCR（qRT-PCR）分析用于测量GDNF和Nurr 1的表达水平。随着时间的延长，PLs-MBs的粒径逐渐增大，浓度和绝对zeta电位逐渐降低。与假手术组相比，6-OHDA增加了苯丙胺诱导的旋转和多巴胺能神经元的丢失。有趣的是，PLs-GDNF-MB或PLs-Nurr 1-MB减少旋转并增加TH和DAT免疫反应性。两种基因的结合导致旋转的稳健减少和多巴胺能神经元的更大增加。使用磁共振成像（MRI）引导的聚焦超声将PLs-GDNF + Nurr 1-MB递送到大脑中可能比单一治疗更有效地治疗PD。
The purpose of this study was to investigate ultrasound‐triggered effects of the glial cell line‐derived neurotrophic factor (GDNF) + nuclear receptor‐related factor 1 (Nurr1)‐polyethylene glycol (PEG)ylated liposomes‐coupled microbubbles (PLs‐GDNF + Nurr1‐MBs) on behavioral impairment and neuron loss in a rat model of Parkinson's disease (PD). The unloaded PEGylated liposomes‐coupled microbubbles (PLs‐MBs) were characterized for zeta potential, particle size, and concentration. 6‐hydroxydopamine (6‐OHDA) was used to establish the PD rat model. Rotational, climbing pole, and suspension tests were used to detect behavioral impairment. The immunohistochemical staining of tyrosine hydroxylase (TH) and dopamine transporter (DAT) was used to assess the neuron loss. Western blot and quantitative real‐time PCR (qRT‐PCR) analysis were used to measure the expression levels of GDNF and Nurr1. The particle size of PLs‐MBs was gradually increased, while the concentration and absolute zeta potential were gradually decreased as the time prolongs. 6‐OHDA increased amphetamine‐induced rotations and loss of dopaminergic neurons as compared to sham group. Interestingly, PLs‐GDNF‐MBs or PLs‐Nurr1‐MBs decreased rotations and increased the TH and DAT immunoreactivity. Combined of both genes resulted in a robust reduction in the rotations and a greater increase of the dopaminergic neurons. The delivery of PLs‐GDNF + Nurr1‐MBs into the brains using magnetic resonance imaging (MRI)‐guided focused ultrasound may be more efficacious for the treatment of PD than the single treatment.