Saponin-Encapsulated Microbubbles Protect Dopaminergic Neurons from MPTP-Induced Oxidative Stress Injury

Zhuxia Zhang,Bingxuan Xu,Tao Lv,Yu Shi,Mengxin Wang,Die Hu,Azhen Hu,Ping Li, Shuping Lin, Shengwei Zhang, Rongquan Yao, Lan Luo,Linlin Wang, Yiping Zhang, Yanni Han,Huiying Hu,Xintao Shuai,Jie Shi,Yun Chen,Tingting Zheng

ADVANCED THERAPEUTICS(2023)

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摘要
Parkinson's disease (PD) is starting at younger ages. In order to reduce the risk of PD in young people, Rb-3 is selected as an active ingredient and assembled into Rb-3 nanoparticles (Rb(3)NPs)encapsulated microbubbles (MBs), shorted for Rb(3)NPs@MBs. This study uses focused ultrasound-mediated Rb(3)NPs@MBs to cross the blood-brain barrier and reach the brain lesions to be intervened in in order to explore the prevention of 1-methyl-4-phenyl-4-piperidinpropionate ester (MPTP)-induced PD by Rb(3)NPs@MBs and its related mechanisms. In the present study, Rb(3)NPs@MBs prevent MPTP-induced tyrosine hydroxylase (TH)-positive cell decreases, decrease TH expression, increase Park2 expression, and decrease expression of & alpha;-synaptonucleoprotein in the pars compactus nigra (SNc). It is found, in vitro study, that Rb(3)NPs treatment significantly reverses MPTP-induced apoptosis and death of PC12/SY5Y cells, which is commonly used mouse/ human neural cell lines. It is also found that Rb(3)NPs@MBs can prevent the production of reactive oxygen species (ROS) in SNc. Finally, it is found that DJ-1 expression decreases after Rb(3)NPs@MBs are introduced. Results suggest that the neuroprotective activity of Rb(3)NPs@MBs may be achieved by increasing the expression of DJ-1 and decreasing the production of ROS. Taken together, these data reveal that Rb(3)NPs@MBs play an important role in preventing memory deficiency in PD.
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关键词
dopaminergic neurons,oxidative stress,microbubbles
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