三氧化二砷诱导血管平滑肌细胞凋亡机制的研究

Study on the Mechanisms of Arsenic Trioxide-induced Vascular Smooth Muscle Cells Apoptosis in vitro

目的探讨三氧化二砷(As2O3)诱导血管平滑肌细胞(VSMCs)凋亡的机制,为其作为药物涂层支架的涂层药物提供理论依据。方法用改良的植块贴壁法体外培养SD大鼠VSMCs,应用MTT法、酶标仪法、流式细胞术等方法观察不同浓度As2O3诱导VSMCs凋亡时裂解液中线粒体跨膜电位(△Ψm)及半胱天冬蛋白酶-3(caspse-3)活性的变化。结果适宜浓度As2O3诱导VSMCs凋亡时△Ψm明显下降,与对照组相比P<0.05;裂解液中caspse-3酶活性明显增高,与对照组相比,P<0.05。结论适宜浓度的As2O3可明显促进VSMCs凋亡,其可能机制是降低△Ψm和激活caspse-3酶。

Objective To discuss the mechanism of As2O3 -induced vascular smooth muscle cells （VSMCs） apoptosis and provide theoretical basis for the use of As203 in drug - eluting stents in future. Methods VSMCs of SD rats were cultured in vitro by modified tissue explants -attached method. NBT reduction test, enzyme -labeling instrument and flow cytometry （FCM） were applied to observe the alteration of mitochondrial membrane potential （ A μm） and activity of caspase -3 when VSMCs apoptosis was induced by different dosage of As2O3. Results The mitochondrial transmembrane potential obviously decreased and the caspase - 3 activity obviously increased when VSMCs apoptosis was induced by appropriate dosage of As2O3 （P 〈 0.05） as compared with control group. Conclusion As2O3 of appropriate dosage can obviously promote apoptosis of VSMCs and the mechanism may be decreasing mitoehondrial transmcmbrane potential and activating caspase - 3.