鼻腔给药雷公藤多苷脂质体对中枢神经炎症所致小鼠行为认知障碍的作用研究

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation

采用薄膜分散法制备雷公藤多苷脂质体(tripterygium glycosides liposome,TPGL),根据其形态结构、平均粒径和包封率等指标优化纳米脂质体的制备方法,并测得粒径为(137.39±2.28)nm,包封率为88.33%±1.82%。脑立体定位注射脂多糖(lipopolysaccharide,LPS)建立中枢神经系统炎症模型小鼠,鼻腔给药TPGL及雷公藤多苷(TPG)21 d。通过检测动物行为学,海马组织HE染色,实时荧光定量PCR和免疫荧光法研究经鼻腔给药TPG与TPGL对LPS诱导的中枢神经系统炎症所致小鼠行为认知障碍的治疗作用。鼻腔给药TPGL相比其原药TPG,对小鼠的鼻黏膜、嗅球、肝肾等损伤更小。通过水迷宫、Y迷宫及筑巢实验,经治疗的小鼠行为表现均得到明显的改善,神经元细胞损伤减轻、炎症及凋亡相关基因(TNF-α、IL-1β、Bax等)和胶质细胞活化标志物(IBA1和GFAP)的表达水平降低。结果表明脂质体通过鼻腔给药不仅减轻了雷公藤多苷经体循环对机体的毒副作用,而且对中枢神经炎症诱导的小鼠认知功能障碍有明显改善作用。

Tripterygium glycosides liposome(TPGL)were prepared by thin film-dispersion method,which were optimized according to their morphological structures,average particle size and encapsulation rate.The measured particle size was(137.39±2.28)nm,and the encapsulation rate was 88.33%±1.82%.The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS).TPGL and tripterygium glycosides(TPG)were administered intranasally for 21 days.The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central nervous system inflammation were estimated by animal behavioral tests,hematoxylin-eosin(HE)staining of hippocampus,real-time quantitative polymerase chain reaction(RT-qPCR)and immunofluorescence.Compared with TPG,TPGL caused less damage to the nasal mucosa,olfactory bulb,liver and kidney of mice administered intranasally.The behavioral performance of treated mice was significantly improved in water maze,Y maze and nesting experiment.Neuronal cell damage was reduced,and the expression levels of inflammation and apoptosis related genes[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),BCL2-associated X(Bax),etc.]and glial activation markers[ionized calcium binding adaptor molecule 1(IBA1)and glial fibrillary acidic protein(GFAP)]were decreased.These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG,and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.