摘要
目的观察载脂蛋白A族Ⅰ型(Apo-A-Ⅰ)基因对动脉粥样硬化(AS)斑块发展的作用。方法将超微超顺磁性氧化铁(USPIO)作为磁性纳米载药系统输送治疗基因,用逆相蒸发法制备带正电荷的磁性脂质体,再将DNA与该脂质体按照1∶7的电荷比形成复合物;将已形成AS斑块的12只大鼠分为实验组和对照组,实验组6只大鼠经尾静脉注入磁性纳米脂质体/DNA复合物,对照组6只大鼠经尾静脉注入不含基因的磁性纳米脂质体复合物,每只动物给药剂量为0.32 ml,给药后立刻在所有动物左侧肾脏附近(体外)绑缚铷铁硼稀土磁铁(场强500mT)进行磁诱导,约4h后将磁铁取下。继续喂养6周后抽血测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL),并将动物处死,取腹主动脉进行油红O染色。结果基因治疗6周后,实验组80层切片中发现斑块10层,脂质条纹面积和纤维斑块面积的百分比分别为9.21%和1.18%;对照组83层切片中发现斑块35层,脂质条纹面积和纤维斑块面积的百分比分别为32.25%和1.66%。实验组与对照组进行斑块率的比较,P<0.01,实验组HDL水平明显升高,实验组肝组织Apo-A-ⅠmRNA水平明显高于对照组。结论DNA与逆相蒸发法制备的磁性脂质体形成的磁性纳米脂质体/DNA复合物在外加磁场导入下可以使Apo-A-Ⅰ基因定向到达肝脏,显著升高血浆HDL水平,降低LDL、TC、TG水平,抑制AS斑块的发展。
Objective To investigate the effect of apoplipoprotein class A typeⅠ （Apo-A-Ⅰ ） gene on development of atherosclerotic （AS） plaques in rats. Methods The magnetic nanoparticle drug carrier system ultrasmall superparamagnetic iron oxide （USPIO） was used to transport the rapentical gene. The magnetoliposome with positive electricity was prepared by antiphase evaporation method, then the liposome and DNA compounds were processed electrostatic interaction, the rate of electric charge between DNA and liposome was 1 ： 7. The 12 rats established into AS plaque models were divided into experimental group （n = 6） and control group （n= 6）. In experimental group, the rats were injected magnetoliposome/DNA compounds containing Apo-A-Ⅰ gene via vena caudalis. In control group, the rats were injected magnetoliposome compounds without gene. The injection dose was 0.32 ml for each rat. After injection, each rat was bound to rubidium-iron-boron rare earth magnet （500 mT field strength） over left kidney about 4 hours. After gene therapy 6 weeks, the TC, TG, HDL and LDL of rats were surveyed, then they were sacrificed, their abdominal aortas were dissociated and stained with oil red O. Results After gene therapy 6 weeks, in experimental group： 10 of 80 sections of abdominal aorta showed AS plaque, the lipid fringe area and fibrous plaque area were 9.21% and 1.18 %; in control group： 35 of 83 sections of abdominal aorta showed AS plaque, the lipid fringe area and fibrous plaque area were 32.25 % and 1.66 %. The occurrence rates of plaque were compared between experimental group and control group, with the statistical significant difference （P 〈 0.01）; The level of HDL in rat blood plasm of experimental group was increased significantly. The mRNA levels of Apo-A-Ⅰ in the livers of experimental group were apparantly higher than that in control group. Conclusion The nanoparticle of magnetoliposome/DNA which is formed by DNA and antiphase evaporated magnetoliposome can promote the Apo-A-Ⅰ geneorientingintoliverundertheinduction of additive magnetic field. It would result in elevating the level of plasma HDL and lowering LDI TC and TG. Thus the development of AS plaque would be inhibited.
出处
《生物医学工程与临床》
CAS
2009年第3期235-240,共6页
Biomedical Engineering and Clinical Medicine
基金
上海市科委重点基金项目(05JC14048)
