辛伐他汀纳米粒的构建及对动脉粥样硬化模型大鼠作用的研究
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大庆油田总医院心内科,黑龙江 大庆 163000

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R-33


Construction of simvastatin nanoparticles and their effect in atherosclerosis model rats
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Affiliation:

Department of Cardiology, Daqing Oilfield General Hospital, Daqing 163000, China

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    摘要:

    目的 构建辛伐他汀纳米给药系统并探讨其对动脉粥样硬化模型大鼠的作用。 方法 制备辛伐他汀纳米粒并通过透射电镜对其进行形态表征;激光共聚焦显微镜检测辛伐他汀纳米粒的细胞摄取能力;构建动脉 粥样硬化大鼠模型,随机分为模型组(Model)、辛伐他汀组(Sim)、辛伐他汀纳米粒组( Sim-LPNs),同时以正常大鼠设立对照组(Control),每组 10 只动物;生化仪检测 TG、TC、LDL-C、HDL-C 水平;HE 染色检测动脉血管病理变化; Western blot 检测 p-AMPK 和 p-ACC 蛋白表达变化。 结果 Sim-LPNs 的形态较为圆整,外观呈均一的球形,平均动力学直径为( 180 ± 23) nm。 与 COU-6 处理相比,COU-6-LPNs 处理的 Caco-2 细胞绿色荧光强度显著增强( P< 0. 01)。 与 Control 组相比,Model 组大鼠 TC、TG、LDL-C 均显著升高,HDL-C 明显降低(P<0. 01);相较于 Model 组, Sim 组 TC 和 LDL-C 显著降低(P<0. 05,P<0. 01);与 Model 组相比,Sim-LPNs 组 TC、TG、LDL-C 均显著降低,HDL-C 明显升高(P<0. 01);与 Sim 相比,Sim-LPNs 大鼠 TC 和 LDL-C 显著降低(P<0. 01)。 Model 组大鼠动脉血管壁粘膜 变性和水肿,在血管壁中出现典型的动脉粥样硬化斑块,并且脂质核心较厚,泡沫明显;Sim 组出现一定改善,但 Sim-LPNs 组改善更为明显。 与 Control 组相比,Model 组动脉血管壁相对斑块面积和相对斑块面积/总面均显著增加(P<0. 01); Sim-LPNs 组相较于 Model 组动脉血管壁相对斑块面积和相对斑块面积/总面明显减小(P<0. 01)。相较于 Control 组,Model 组大鼠肝组织 p-AMPK 和 p-ACC 蛋白表达均显著下调(P<0. 01);与模型组相比,Sim 组 p- AMPK 蛋白表达显著上调(P<0. 05),Sim-LPNs 组 p-AMPK 和 p-ACC 蛋白表达显著上调(P<0. 01,P<0. 05);与 Sim 组相比,Sim-LPNs 组 p-AMPK 蛋白表达上调更明显(P<0. 01)。 结论 辛伐他汀纳米粒具有较好的抗动脉粥样硬化效果,该作用可能与其增强小肠细胞吸收和激活肝细胞 AMPK-ACC 信号通路调节血脂水平有关。

    Abstract:

    Objective To construct a simvastatin nano drug delivery system and explore its effect on atherosclerosis model rats. Methods Laser confocal microscopy was used to detect the cell uptake capacity of simvastatin nanoparticles. Rats were randomly divided into a model group (Model), simvastatin group (Sim), simvastatin nanoparticle group (Sim-LPNs), and control group (Control, normal rats), with 10 animals per group. A biochemical analyzer was used to detect TG, TC, LDL-C, and HDL-C levels. HE staining was used to detect pathological changes in arteries and vessels. Western blot was used to detect changes in p-AMPK and p-ACC protein levels. Results Sim-LPNs had a uniform spherical appearance with a mean dynamic diameter of 180 ± 23 nm. Compared with COU-6 treatment, the green fluorescence intensity of Caco-2 cells treated with COU-6-LPNs was significantly enhanced (P<0. 01). Compared with the Control group, the TC, TG and LDL-C levels in the Model group were significantly increased, and HDL-C was significantly decreased (P<0. 01). Compared with the Model group, the Sim group had significantly lower TC and LDL-C levels (P< 0. 01 or P<0. 05). Compared with the Model group, the Sim-LPNs group had significantly reduced TC, TG, and LDL-C levels, as well as significantly increased HDL-C levels (P<0. 01). Compared with the Sim group, TC and LDL-C levels in Sim-LPNs rats were significantly reduced ( P< 0. 01). In the Model group, mucosal degeneration, edema, and typical atherosclerotic plaques with a thick lipid core and foam cells were observed in the arterial blood vessel walls. The Sim group showed some improvement, but the Sim-LPNs group had a more obvious improvement. Compared with the Control group, the relative plaque area and relative plaque area / total surface of the arterial blood vessel wall of the Model group were significantly increased (P<0. 01). Compared with the Model group, the relative plaque area and the relative plaque area / total surface of the arterial wall of the Sim-LPNs groups were significantly reduced (P<0. 01). Compared with the Control group, the expressions of p-AMPK and p-ACC proteins in the liver tissues of the Model group were significantly downregulated ( P < 0. 01). Compared with the model group, the expression of p-AMPK protein in the Sim group was significantly increased (P< 0. 05), and the expressions of p-AMPK and p-ACC proteins in the Sim-LPNs groups were significantly increased (P<0. 05 or P<0. 01). Compared with the Sim group, p-AMPK protein expression in the Sim-LPNs groups was significantly upregulated (P<0. 01). Conclusions Simvastatin nanoparticles have a good anti-atherosclerotic effect, which may be related to the enhanced absorption of small intestinal cells and activation of the liver cell AMPK-ACC signaling pathway to regulate blood lipid levels.

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韩金霞,朱亚南,王金文,王吉佳,李 迪,杨静波.辛伐他汀纳米粒的构建及对动脉粥样硬化模型大鼠作用的研究[J].中国比较医学杂志,2020,30(11):78~83.

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  • 收稿日期:2020-05-07
  • 在线发布日期: 2020-12-25
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