摘要
目的对神经生长因子(nerve growth factor,NGF)和NGF脂质体(NGF-SSL)鼻腔给药的药效学进行研究,并与NGF静脉给药相比较。方法鹅膏蕈氨酸(ibotenicacid,IBO)大鼠Meynert核注射制造阿尔茨海默氏病(alzheimer'sdisease,AD)模型,以生理盐水Meynert核注射作为假手术对照组,通过水迷宫试验,跳台实验和乙酰胆碱酯酶(AchE)组织化学染色来评价AD模型。并应用此模型采用同样方法研究NGF静脉给药,NGF和NGF-SSL鼻腔给药后的药效。结果AD模型经鉴定能够应用于药效研究。NGF鼻腔给药药效优于NGF静脉注射,NGF经脂质体包载后药效进一步提高。NGF-SSL鼻腔给药后能明显保护胆碱能神经元免受损伤,动物游泳时间缩短,跳台潜伏期延长,AchE染色积分光密度接近正常大鼠。结论鼻腔给药能够实现药物给药途径上的脑靶向,药物经脂质体包载后能明显增加其脑摄入,提高药效。
Abstract
OBJECTIVE To study the pharmacodynamic parameters of NGF and NGF sterically stabilized liposomes(NGF-SSL) via nasal administration and compare with NGF intravenous inject. METHODS Alzheimer's disease (AD) model was made by Meynert nucleus injected with ibotenic acid(IBO), and was evaluated by the water maze, footshock avoidance and AchE Histochemistry staining tests. The pharmacodynamic parameters of NGF (iv) and NGF, NGF-SSL (na) were studied by using the AD model. RESULTS AD model was appraised to be suitable for studying the pharmacology efficacy of NGF. The pharmacodynamics of NGF via nasal administration was better than that of NGF intravenous inject, and that of NGF-SSL via nasal administration was further improved. Nasal administration protected the cholinergic neuron from being damaged by IBO, the swim time of the rats was shorten, and the footshock avoidance latency was extended, the integral spectro-density of AchE staining was near to that of control rats.CONCLUSION Nasal administration is a better way to target the brain, and the brain uptake of drug modified with lioposomes would be increased, the pharmacodynamics would be improved.
关键词
神经生长因子 /
脂质体 /
鼻腔给药 /
药效
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Key words
nerve growth factor(NGF) /
liposome /
nasal administration /
pharmacodynamics
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谢英;杜熠;耿兴超;侯新朴.
神经生长因子脂质体大鼠鼻腔给药的药效学研究[J]. 中国药学杂志, 2005, 39(10): 742-745
XIE Ying;DU Yi;GENG Xing-cho;HOU Xin-pu.
Study on treatment of AD by NGF liposomes via nasal administration [J]. Chinese Pharmaceutical Journal, 2005, 39(10): 742-745
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参考文献
[1］Frey WH， Liu J， Chen X，et al. Delivery of 125I-NGF to the brain via the olfactory route[J］.Drug Delivery，1997，4(2)：87.
[2］Gizurarson S， Thorvaldsson T， Sigurdsson P，et al. Selective delivery of insulin into the brain： intraolfactory absorption[J］.Int J Pharm，1996，140(1)：77.
[3］魏小龙，张永祥.老年性痴呆动物模型研究进展[J］.中国药理学通报，2000，16(4)：372.
[4］Pizzo DP， Thal LJ. Intraparenchymal nerve growth factor improves behavioral deficits while minimizing the adverse effects of intracerebroventricular delivery[J］.Neuroscience，2004，124(4)：743.
[5］Morimoto K， Yoshimi K， Tonohiro T， et al.Co-injection of α-amyloid with ibotenic acid induces synergistic loss of rat hippocampal neurons[J］.Neuroscience， 1988，84(2)：479.
[6］Whitehouse PJ， Price DL， Struble RG， et al. Alzheimer′s disease and senile dementia： loss of neurons in the basal forebrain[J］.Science，1982，215(4537)：1237.
[7］George P, Charles W. The rat brain in stereotaxic coordinates[M］. 3ed. New York：Academic Press，1991.
[8］徐叔云，卞如濂，陈修. 药理学实验方法[M］. 第三版， 北京：人民卫生出版社，北京，2003：826.
[9］Hedreen JC， Bacon SJ， Price DL. A modified histochemical technique to visualize acetylcholinesterase-containing axons[J］.J Histochem Cytochem，1985，33(2)：134.
[10］徐滨，陈俊抛，周光斗，等.去松果体对大鼠学习记忆及大脑皮质胆碱能纤维的影响[J］.中华神经科杂志，2000，33（3）：153.
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脚注
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基金
国家自然科学基金资助项目(30171114)
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