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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 observe the effect of apolipoprotein A type Ⅰ (Apo-A-Ⅰ) gene on the development of atherosclerosis (AS) plaque. Methods Super microplasma paraffin magnetic iron oxide (USPIO) was used as magnetic nanocarrier system to deliver therapeutic gene. The reverse phase evaporation method was used to prepare positively charged magnetic liposomes. 12 rats with AS plaque were divided into experimental group and control group. Six rats in the experimental group were injected with magnetic nano-liposome / DNA complex through the tail vein, and six rats in the control group Rats were injected via the tail vein with gene-free magnetic nanoliposome complexes at a dose of 0.32 ml per animal. Immediately after administration, all the animals were bound to NdFeB magnets in the vicinity of the left kidney (in vitro) Strong 500mT) for magnetic induction, the magnet removed after about 4h. Blood samples were taken for 6 weeks and then for serum TC, TG, HDL and LDL. The animals were sacrificed and the abdominal aorta was taken for oil red O staining. Results Six weeks after gene therapy, plaques were found in 80 slices of experimental group, with the percentage of lipid stripe area and fibrous plaque area being 9.21% and 1.18%, respectively. In control group, 35 plaques were found in 83- The percentages of lipid stripe area and fiber plaque area were 32.25% and 1.66%, respectively. The plaque rate of the experimental group and the control group were compared, P <0.01, the experimental group HDL levels were significantly increased, the experimental group liver Apo-A-ⅠmRNA levels were significantly higher than the control group. Conclusion Magnetic nanoparticle liposomes / DNA complexes formed by magnetic liposome prepared by DNA and reverse phase evaporation can lead Apo-A-Ⅰ gene to reach the liver under the condition of applied magnetic field, significantly increase plasma HDL level and decrease LDL , TC, TG levels, inhibit the development of AS plaque.