Lu Cui-Tao, Jin Rong-Rong, Jiang Yi-Na, Lin Qian, Yu Wen-Ze, Mao Kai-Li, Tian Fu-Rong, Zhao Ya-Ping, Zhao Ying-Zheng
The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China ; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
Drug Des Devel Ther. 2015 Apr 7;9:1955-62. doi: 10.2147/DDDT.S77237. eCollection 2015.
The aim of this study was to investigate the protective role of intranasally administered substance P-loaded gelatin nanoparticles (SP-GNPs) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in vitro and in vivo, and to provide a new strategy for treating brain pathology, such as Parkinson's disease.
SP-GNPs were prepared by a water-in-water emulsion method, and their stability, encapsulating efficiency, and loading capacity were evaluated. PC-12 cells were used to examine the enhancement of growth and inhibition of apoptosis by SP-GNPs in vitro using MTT assays. In the in vivo study, hemiparkinsonian rats were created by intracerebroventricular injection of 6-OHDA. The rats then received intranasal SP-GNPs daily for 2 weeks. Functional improvement was assessed by quantifying rotational behavior, and the degree of apoptosis was assessed by immunohistochemical staining for caspase-3 in the substantia nigra region.
PC-12 cells with 6-OHDA-induced disease treated with SP-GNPs showed higher cell viability than their untreated counterparts, and cell viability increased as the concentration of substance P (SP) increased, indicating that SP could enhance cell growth and inhibit the cell apoptosis induced by 6-OHDA. Rats with 6-OHDA-induced hemiparkinsonism treated with SP-GNPs made fewer rotations and showed less staining for caspase-3 than their counterparts not treated with SP, indicating that SP protects rats with 6-OHDA-induced hemiparkinsonism from apoptosis and therefore demonstrates their functional improvement.
Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.
本研究旨在探讨经鼻给药的载P物质明胶纳米粒（SP-GNPs）在体外和体内对6-羟基多巴胺（6-OHDA）诱导的细胞凋亡的保护作用，并为治疗帕金森病等脑部疾病提供新策略。
采用水包水乳液法制备SP-GNPs，并对其稳定性、包封率和载药量进行评估。利用MTT法，使用PC-12细胞检测SP-GNPs在体外对细胞生长的促进作用和对细胞凋亡的抑制作用。在体内研究中，通过脑室内注射6-OHDA建立偏侧帕金森病大鼠模型。然后，大鼠每天经鼻给予SP-GNPs，持续2周。通过量化旋转行为评估功能改善情况，并通过免疫组织化学染色检测黑质区域caspase-3的表达来评估细胞凋亡程度。
用SP-GNPs处理的6-OHDA诱导疾病的PC-12细胞比未处理的细胞具有更高的细胞活力，并且细胞活力随着P物质（SP）浓度的增加而增加，表明SP可以促进细胞生长并抑制6-OHDA诱导的细胞凋亡。用SP-GNPs处理的6-OHDA诱导的偏侧帕金森病大鼠比未用SP处理的大鼠旋转次数更少，caspase-3染色也更少，表明SP可保护6-OHDA诱导的偏侧帕金森病大鼠免于细胞凋亡，从而证明其功能得到改善。
经鼻递送SP-GNPs在体外和体内均可保护细胞免受6-OHDA诱导的凋亡。
