单次大剂量阿托伐他汀对不稳定性心绞痛患者血管内皮功能及Rho激酶活性的影响

Effect of a High Single Dose Atorvastatin on Endothelial Function and Rho Kinase Activity in Patients With Unstable Angina

目的:通过观察单次大剂量阿托伐他汀对不稳定性心绞痛患者血管内皮功能及外周血白细胞Rho激酶活性的影响,探讨他汀改善不稳定性心绞痛患者血管内皮功能的可能机制。方法:入选2012-08至2014-02入住我院的不稳定性心绞痛患者78例,入院当日给予阿托伐他汀80 mg一次顿服。分别于服药前及服药后12 h以超声测反应性充血前后肱动脉内径(FMD)的变化,以免疫印迹法(Western Blot)测外周血白细胞肌球蛋白轻链磷酸酶的肌球蛋白结合亚单位(MYPT1)及在Thr853位上磷酸化的MYPT(1p-MYPT1^(Thr853))蛋白表达,以p-MYPT1^(Thr853)占总MYPT1的百分比表示Rho激酶的活性。结果:患者服用阿托伐他汀80 mg 12 h后,FMD较治疗前增加28.15%[(6.50±1.68)%vs(8.33±1.93)%,P<0.001],外周血白细胞Rho激酶活性较治疗前降低32.78%[(58.91±5.22)%vs(39.6±3.85)%,P=0.002]。结论:大剂量阿托伐他汀能快速改善不稳定性心绞痛患者的血管内皮功能,RhoA/Rho激酶通路抑制参与他汀类药物快速改善血管内皮功能的作用。

Objective： To explore the possible mechanism of statins improving endothelial function via observing the effect of a high single dose atorvastatin on endothelial dysfunction and peripheral blood leucocyte Rho kinase activity in patients with unstable angina （UA）. Methods： A total of 78 consecutive UA patients admitted in our hospital from 2012-08 to 2014-02 were enrolled. The patients received a single dose of atorvastatin 80 mg on the day of admission. Flow-mediated vasodilation （FMD） of brachial artery was examined by high-resolution ultrasound at before and 12 hours after medication. Protein expression of phospho-speciifc Thr853-MYPT1 （p-MYPT1Thr853） and MYPT1 was measured by Western blot analysis; peripheral blood leukocyte Rho kinase activity was assayed by the proportion of phospho-Thr853 in myosin binding subunit of light chain phosphatase （MYPT1）. Results： Compared to prior medication, with atorvastatin 80 mg for 12 hours, FMD was increased 28.15% as （6.50 ±1.68） % vs （8.33 ± 1.93） %,P〈0.001 and peripheral blood leucocyte Rho kinase activity was decreased 32.78% as （58.91 ± 5.22） % vs （39.6 ± 3.85 ） %,P=0.002.Conclusion： High dose atorvastatin could rapidly improve vascular endothelial dysfunction in UA patients. inhibiting of RhoA/Rho kinase pathway may involve in the effect of statins improving endothelial function.