依泽替米贝对血管平滑肌源性荷脂细胞胆固醇蓄积的影响  

Effect of Ezetimibe on Cholesterol Accumulation in Loaded-Lipid Cells Derived From Vascular Smooth Muscle Cells

作　　者：高治平[1] 于伟霞[1] 袁皓瑜[1] 朱炳阳[1] 夏承来[1] 孙少卫[1] 廖端芳[1] 

机构地区：[1]南华大学药物药理研究所,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2008年第1期25-28,共4页Chinese Journal of Arteriosclerosis

基　　金：湖南省教育厅课题(04C539)

摘　　要：目的观察依泽替米贝对血管平滑肌源性的荷脂细胞胆固醇蓄积的影响。方法采用20mg/L胆固醇、β-环糊精混合物处理培养的大鼠主动脉平滑肌细胞建立荷脂细胞模型,用不同浓度的依泽替米贝(3、10μmol/L和30μmol/L)处理荷脂细胞24h,随后用30μmol/L的依泽替米贝处理荷脂细胞不同的时间(0、6、12、24h和48h)。通过高效液相色谱仪检测细胞内总胆固醇、游离胆固醇的含量;油红O染色观察细胞内胆固醇蓄积的情况。结果(1)3、10μmol/L和30μmol/L依泽替米贝处理荷脂细胞后,细胞内总胆固醇含量分别为110.8±3.56、90.5±2.30mg/g和60.9±1.86mg/g,游离胆固醇含量分别为85.5±3.12、74.6±2.89mg/g和53.8±1.56mg/g;与模型组比较,中、高剂量组总胆固醇、游离胆固醇差异均有显著性(P<0.05),随浓度升高,两者都有降低趋势(趋势性χ2检验,P=0.007),且30μmol/L组作用最佳。(2)选择30μmol/L依泽替米贝处理荷脂细胞0、6、12、24h和48h,各时间点细胞内总胆固醇含量分别为120.1±2.37、117.9±3.05、80.3±2.81、69.2±1.56mg/g和72.1±2.98mg/g,随着时间的延长,总胆固醇浓度逐渐降低,两者呈负相关(r=-0.776,P<0.05);游离胆固醇含量分别为92.9±2.11、90.7±3.76、71.4±2.57、60.1±1.21mg/g和64.2±2.48mg/g,随着时间的延长,游离胆固醇浓度逐渐降低,两者呈负相关(r=-0.786,P<0.05);与0h组比较,12、24h和48h组差异均有显著性(P<0.01),并呈时间依赖性,24h组效果最显著。结论依泽替米贝能降低血管平滑肌源性荷脂细胞胆固醇蓄积。Aim To investigate the effect of Ezefimibe on cholesterol accumulation in loaded-llpid cells derived from vascular smooth muscle cells （VSMC）. Methods Loaded-lipid cells medel were established by 20 mg/L Chol： Mβ3CD treated VSMC. Loaded-lipid cells were respectively treated with different concentration of ezetimibe （0, 3, 10, 30 μmol/L） for 24 h, and with 30μmol/Lofezetimibe for different time （0, 6, 12, 24, 48h）. The concentration of total cholesterol （TG） and free cholesterol （FC） were detected by high performance liquid chromatography （HPLC）. Cholesterol accumulation in cells were observed by oil red O staining. Results （1） Intra-ceUularTGwerel10.8±3.56,90.5± .2.30,60.9±1.86mg/g and FC were 85.5±3.12,74.6 ± 2.89,53.8± 1.56 mg/g, respectively with loaded-llpid cells treated with different concentration of ezetimibe. Compared with model group, there was significant difference in medium-dose and high-dose groups（P 〈 0.05）, TG and FC had a reducing trend with rising drug concentration（tendency χ^2 = 11.56, P = 0.007） and the best drug concentration was 30 μmol/L. （2） Treated loaded-lipid cells for different time （0, 6, 12, 24, 48 h） with 30 μmol/L ezetimibe, the content of TG were 120.1 ± 2.37, 117.9±3.05, 80.3± .2.81, 69.2± 1.56, 72.1 ±2.98 mg/g and FC were 92.9± 2.11, 90.7 ± 3. 76, 71.4±2.57, 60.1± 1.21, 64.2 ± 2.48 mg/g respectively. TG and FC gradually decreased with treated time, andhothof them had negative correlations with treated time （ r = - 0.776, P 〈 0.05 and r = - 0.786, P 〈 0.05 respectively ）. Compared with O h group, there was significant difference for FC in 12 h, 24 h and 48 h groups （ P 〈 0.01 ）.There was time-depended tendency for ezetimibe and it was best for 24 hours. Conclusion Ezetimibe decrease cholesterol accumulation in vascular smooth muscle cells.

关 键 词：药理学 依泽替米贝 血管平滑肌细胞 胆固醇蓄积 动脉粥样硬化 油红O染色法 高效液相色谱法 

分 类 号：R96[医药卫生—药理学]