柔性纳米脂质体介导脑源性神经营养因子经鼻给药治疗帕金森病的研究

Experimental Study on Flexible Nano Liposome Mediated Brain-derived Neurotrophic Factor Treatment of Parkinson Disease by Nasal Administration

关键词:  柔性纳米脂质体  脑源性神经营养因子  帕金森病

Key words:  flexible nano liposomes  brain-derived neurotrophic factor(BDNF)  Parkinson disease

摘要:

目的 研究柔性纳米脂质体介导脑源性神经营养因子(brain derived neurotrophic factor，BDNF)经鼻给药治疗帕金森病的有效性及安全性。方法 采用注入法制备BDNF柔性纳米脂质体(BDNF-FNL)，建立大鼠帕金森模型，将建模成功的大鼠随机分为模型组、BDNF溶液组及BDNF-FNL组，并以正常大鼠作空白对照，分别经鼻给药后于0.5，1，1.5，2 h测定BDNF在脑组织中的含量变化，以鼻黏膜组织病理改变初步判断该途径给药的鼻腔安全性，通过实验组大鼠的行为学变化、黑质酪氨酸羟化酶免疫阳性神经元的变化以及脑内纹状体3种单胺类神经递质(多巴胺、多巴柯和高香草酸)的含量变化评价其对帕金森病模型大鼠多巴胺神经元的修复作用。结果 BDNF-FNL组BDNF的脑组织浓度约是BDNF溶液组的3倍；柔性脂质体经鼻给药后安全性较高，对鼻黏膜无明显损伤；BDNF-FNL组的大鼠行为学改善效果优于BDNF溶液组；TH免疫组化结果表明，柔性纳米脂质体能更好的介导BDNF进入脑部发挥对多巴胺神经元保护作用；且BDNF-FNL组大鼠纹状体中3种单胺类神经递质的含量明显地高于BDNF溶液组及模型组。结论 柔性纳米脂质体能更好地介导BDNF经鼻入脑发挥对帕金森病模型大鼠多巴胺神经元的修复作用，且对鼻黏膜的安全性较好。

Abstract:

OBJECTIVE To study on the effectiveness and safety of flexible nano liposome mediated brain derived neurotrophic factor (BDNF) for the treatment of Parkinson disease by nasal administration. METHODS Flexible nano liposome of BDNF(BDNF-FNL) was prepared by injection. The Parkinson disease model rats were established and the successful model rats were randomly divided into three groups: model group, BDNF solution group, BDNF flexible nano liposome group, and using normal rats as control group. After drug was intranasal administrated, the content of BDNF in brain was measured in 0.5, 1, 1.5, 2 h, respectively. The pathological change of nasal mucosa was used to preliminary judgment of the safety of intranasal administration. The dopamine neuroreparable effects of Parkinson disease model rats was evaluated by the behavioral changes of experimental group rats, the immune positive neurons changes of substantia nigra TH, and the content changes of 3 monoamine neurotransmitters of brain striatum (DA, DOPAC and HVA). RESULTS The BDNF concentration of brain tissue of BDNF-flexible nano liposome group was about 3 times than BDNF solution group. Flexible nano liposome was high security through intranasal administration with no significant damage to the nasal mucosa. The behavior of rats was improved in BDNF flexible nano liposome group which were better than BDNF solution group. TH immunohistochemical results showed that flexible nano liposome could better mediate BDNF enter the brain and play the protective effect on DA neurons. And the contents of 3 kinds of monoamine neurotransmitters in rats’ striatum of BDNF flexible nano liposome group were apparently higher than that in BDNF solution group and model group. CONCLUSION Flexible nano liposome can mediate BDNF through nose to brain and play a repair action on dopamine neurons in Parkinson disease model rat, and shows good security of nasal mucosa.