阿托伐他汀对高胆固醇血症患者低密度脂蛋白受体功能影响的研究

目的观察高胆固醇血症患者在服用阿托伐他汀前后低密度脂蛋白受体功能的变化,并探讨其调节低密度脂蛋白代谢的机制。方法以临床诊断为高胆固醇血症的患者为研究对象,以阿托伐他汀为工具药,对患者服药前后进行常规体格检查,血脂等生化指标测定。分离培养高胆固醇血症患者外周血淋巴细胞,加入异硫氰酸荧光素标记低密度脂蛋白,分别于4℃和37℃孵育,流式细胞仪检测其细胞表面结合、摄取低密度脂蛋白的平均荧光强度,观察患者服药前后淋巴细胞结合与摄取低密度脂蛋白的变化。结果服用阿托伐他汀4周后,与服药前比较高胆固醇血症患者血浆低密度脂蛋白胆固醇和总胆固醇水平明显降低[低密度脂蛋白胆固醇水平：（3.63±1.01）mmol.L-1vs（2.3±2.02）mmol.L-1,P〈0.001;总胆固醇水平：（5.69±1.28）mmol.L-1vs（4.2±2.06）mmol.L-1,P〈0.001],高密度脂蛋白胆固醇在血浆中的比例明显升高[（50%±16%）vs（59%±17%）,P=0.02],而且患者淋巴细胞表面低密度脂蛋白受体对低密度脂蛋白的结合与摄取活性在服药后也出现了明显提高[低密度脂蛋白受体表达量：（129.7±104.0）vs（236.2±108.7）,P〈0.05;低密度脂蛋白受体结合能力：（43.6±35.8）vs（86.4±126.8）,P〈0.05;低密度脂蛋白受体内化能力（53.4±63.2）vs（102.5±101.4）,P〈0.05]。结论本研究结果显示阿托伐他汀可显著降低高胆固醇血症患者血浆低密度脂蛋白胆固醇和总胆固醇水平,提高高密度脂蛋白胆固醇在血浆中的比例;同时上调低密度脂蛋白受体的表达,提高低密度脂蛋白受体对低密度脂蛋白结合与内化能力;进而达到综合调整低密度脂蛋白代谢水平的药理作用。

Effect of atorvastatin on low-density lipoprotein receptor in patients with hypercholesterolemia

Objective To analyze the binding and internalization activity of the low-density lipoprotein receptor（LDL-R） protein in hypercholesterolemia patients before and after the treatment with atorvastatin and explore the mechanism of atorvastatin on LDL metabolism.Methods Hypercholesterolemia patients were clinically diagnosed,and given routine medical examinations and biochemical examinations before and after the treatment with atorvastatin.Lymphocytes were isolated from the whole blood.The lymphocytes were incubated with fluorescein isothiocyanate labeled LDL at 4℃ and 37℃ for 2 h respectively.The binding and internalization of LDL to LDL receptors were detected by flow cytometer before and after the administration of atorvastatin.Results Serum LDL-C and total cholesterol（TC） level decreased significantly[LDL-C level：（3.63±1.01）mmol·L-1vs（2.3±2.02）mmol·L-1,P0.001;TC level：（5.69±1.28） mmol·L-1vs（4.2±2.06）mmol·L-1,P0.001].The lymphocyte LDL-R binding and internalization activity in hypercholesterolemia patients were significantly lower than before the treatment.[LDLR expression level：（129.7±104.0） vs（236.2±108.7）,P0.05;LDLR binding activity：（43.6±35.8） vs（86.4±126.8）,P0.05;LDLR internalization level：（53.4±63.2） vs（102.5±101.4）,P0.05].Conclusion Atorvastatin can decrease the serum LDL-C and TC level,raise the propotion of HDL-C,improve the function of LDL receptors,and therefore improve the metablism of LDL-C.