抗动脉粥样硬化基因疫苗经鼻腔免疫黏膜毒性的初步评价  

Preliminary safety evaluation of an anti-atherosclerosis DNA vaccine after repeated intranasal administration

作　　者：蔡丹宁[1] 吴瑞[1] 袁喜英[1] 宗莉[1] 

机构地区：[1]中国药科大学药物制剂研究所,江苏南京210009

出　　处：《药学与临床研究》2009年第3期182-186,共5页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金(No.30572272)

摘　　要：目的:考察抗动脉粥样硬化基因疫苗经鼻腔接种免疫的黏膜毒性。方法:以壳聚糖为基因载体,制备载基因疫苗的壳聚糖纳米粒。对高脂家兔模型滴鼻免疫6次,28周时取鼻黏膜及肺部组织行组织病理学检查,扫描电镜观察鼻黏膜纤毛的超微结构变化。结果:基因疫苗经鼻腔免疫可以显著诱导抗体,延缓动脉粥样硬化的发展。组织病理学检查表明,鼻黏膜及肺部组织形态正常。黏膜纤毛超微结构的扫描电镜观察表明,鼻黏膜纤毛排列有序,无断裂、脱落、倒伏等异常现象。结论:基因疫苗经鼻腔接种未致黏膜及纤毛损伤,鼻腔给药有潜力发展为一种新的接种途径。Objective： To evaluate the safety of an antiatherosclerosis DNA vaccine following repeated intranasal vaccination. Methods： Chitosan was used as carrier material to prepare DNA vaccine loaded chitosan nanoparticles. The chitosan/DNA nanoparticles were given intranasally to rabbit as a model of atheroselerosis 6 times consecutively. Then the rabbits were killed at week 28 and the septal mucosae and lung tissues were removed for histopathological examination. Mucosae of anterior nasal segment and turbinate were observed by scanning electron microscope （SEM） for ultrastruetural changes in mucoeilia. Results： Significant serum antibodies against CETP were detected in the rabbit model, and the progression of atherosclerosis was significantly attenuated. Moreover, there was no sign of damage noted in nasal mueosae and lung tissues from the group receiving chitosan/DNA nanoparticles, and the ciliary lining was regular without function or mucosal breakage damage , loss or disorientation, as revealed by SEM. Conclusions： No ciliary dyswas observed after intranasal vaccination of chitosan/DNA nanoparticles. Thus, intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

关 键 词：鼻腔 免疫 基因疫苗 黏膜毒性 动脉粥样硬化 

分 类 号：R967[医药卫生—药理学] R915[医药卫生—药学]