β受体阻滞剂对体外培养血管内皮细胞增生及凋亡的影响

The effect of β-blockers on proliferation and apoptosis of human umbilical vein endothelial cells in vitro culture

目的了解普萘洛尔、阿替洛尔、醋丁洛尔及噻吗洛尔对体外培养的血管内皮细胞增生及凋亡的影响。方法对人脐静脉血管内皮细胞进行体外培养,分别加入9种浓度的4种药物,设立阴性及阳性对照,采用cell counting kit-8(CCK-8)法检测细胞增生,Annexin-V FITC/PI双染法检测细胞凋亡。结果 1同一药物不同浓度之间抑制率比较:普萘洛尔和阿替洛尔结果一致,各个浓度之间抑制率P均<0.05;醋丁洛尔和噻吗洛尔结果一致,3.125μmol/L与12.5μmol/L及12.5μmol/L与50μmol/L抑制率P均>0.05,其余浓度间抑制率P均<0.05。2同一浓度的不同药物之间抑制率比较:在200、100、50μmol/L 3种浓度时,普萘洛尔与阿替洛尔、醋丁洛尔及噻吗洛尔抑制率比较P均<0.05,后3种药物抑制率比较P均>0.05;在25μmol/L浓度时,普萘洛尔与醋丁洛尔抑制率比较P均<0.05;其余药物抑制率比较P均>0.05。在12.500、6.250、3.125、1.562 5、0.781 3μmol/L这5种浓度中,同一浓度的不同药物抑制率比较P均>0.05。3对细胞凋亡的诱导:普萘洛尔、阿替洛尔与阴性对照组凋亡率比较P均<0.05;阿替洛尔、普萘洛尔、醋丁洛尔和噻吗洛尔与二氯化钴组凋亡率比较P均<0.05;而阿替洛尔、普萘洛尔、醋丁洛尔和噻吗洛尔4种药物凋亡率比较P均>0.05。结论 4种药物均可抑制细胞增生,普萘洛尔作用最强,且随着药物浓度增加抑制作用也明显增强;4种药物均可诱导细胞凋亡,但彼此之间无明显差异。

Objective To observe the influence of propranolol, atenolol, acebutolol and timolol on the proliferation and apoptosis of human umbilical vein endothelial cells in vitro culture. Methods Human umbilical vein endothelial cells were cultured in vitro. Four kinds of the drugs, each with 9 different concentrations and the negative and positive control were added. Cell counting Kit-8 （CCK-8） method was used to detect cell proliferation and annexin-V FITC/PI double staining method was used to detect cell apoptosis. Results The inhibition rate between different drug concentrations of one drug： all concentrations of propranolol and atenolol presented significant difference （P〈0.05） of the inhibition rate between each other. With the concentrations of 3.125 μmol/L and 12.5 μmol/L, 12.5 μmol/L and 50 μmol/L of acebutolol and timolol both presented significant difference （P〈0.05） of the inhibition rate between each other. The other concentrations of acebutolol and timolol both presented no significant difference （P〈0.05） of the inhibition rate between each other. Inhibition rates between different drugs of the same concentration： with the concentrations of 200 μmol/L, 100 μmol/L and 50 μmol/L, inhibition rates of propranolol group was significantly higher than that of atenolol group, acebutolol group and timolol group （P〈0.05）, the inhibition rates of atenolol group, acebutolol group and timolol group had no significantly differences between each other （P〉0.05）. With the concentrations of 25 μmol/L, inhibition rates of propranolol group was significantly higher than that of acebutolol group （P〈0.05）, other drug groups had no significant differences between each other （P〉0.05）. With the concentrations of 12.5 gmol/L, 6.25 μmol/L, 3.125 μmol/L, 1.5625 μmol/L and 0.7813 μmol/L, inhibition rates of propranolol group, atenolol group, acebutolol group and timolol group had no significant differences between each other （P〉0.05）. The apoptosis rate of human umbilical vein endothelial cells： the apoptosis rate ofpropranolol group and atenolol group were both significantly higher than that of negative group （P〈0.05）; the apoptosis rate of propranolol group, atenolol group, acebutolol group and timolol group were all significantly higher than that of cobalt dichloride group （P〈0.05）; the apoptosis rate of propranolol group, atenolol group, acebutolol group and timolol group had no significant differences between each other （P〉0.05）. Conclusion Four kinds of β-blockers can inhibit human umbilical vein endothelial cells proliferation, propranolol has the strongest effect, the higher concentration, the better effect. Four kinds of β-blockers can induce human umbilical vein endothelial cells apoptosis, however, there were no significantly differences