紫杉醇/比伐卢定球囊涂层复合物对HCASMC和HCAEC体外增殖活性的影响  

Influence of paclitaxel-bivalirudin balloon coating complex on proliferative activities of human coronary artery smooth muscle cells and human coronary artery endothelial cells in vitro

作　　者：王凯 王显[2,3] 王渊 王宁勃 Wang Kai;Wang Xian;Wang Yuan;Wang Ningbo(Department of Emergency,First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;不详)

机构地区：[1]天津中医药大学第一附属医院急症部,天津300193 [2]北京中医药大学东直门医院心内科,北京100700 [3]北京中医药大学心血管病研究所,北京100700 [4]北京中医药大学孙思邈医院心内科,铜川727031

出　　处：《中国循证心血管医学杂志》2023年第7期781-784,共4页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家自然科学基金面上项目(81774058);北京中医药大学2018年度校级青年教师科研项目(2018-BUCMXJKY)。

摘　　要：目的探讨紫杉醇/比伐卢定复合物(络风宁0号)对体外培养的人冠状动脉平滑肌细胞(HCASMC)和人冠状动脉内皮细胞(HCAEC)增殖的影响,为新一代中药单体复合药物涂层球囊(DCB)的研发提供依据。方法将HCASMC和HCAEC体外培养并传代至4~6代,根据药物干预分为紫杉醇(1μmol/L)组和紫杉醇/比伐卢定(PB)组,其中PB组所采用为1μmol/L紫杉醇配伍不同浓度比伐卢定(1/256、1/128、1/64、1/32、1/16、1/8、1/4、1/2和1 mg/ml),48 h后用MTT法检测各组HCASMC和HCAEC细胞的增殖活力,以筛选出紫杉醇与比伐卢定之间的最佳配比,抑制HCASMC增殖的同时不影响甚至促进HCAEC增殖,为内皮友好型中药单体复合DCB的研发提供实验数据支持。结果同紫杉醇组相比,PB组中紫杉醇配伍低浓度比伐卢定(1/256 mg/ml)即可增强紫杉醇对HCASMC增殖的抑制作用,该作用随比伐卢定浓度增高而增强,呈浓度依赖关系,差异有统计学意义(P<0.05);紫杉醇配伍低浓度比伐卢定(1/256和1/128 mg/ml)时对HCAEC增殖无影响(P>0.05),但比伐卢定浓度>1/128 mg/ml时对HCAEC的抑制作用较紫杉醇组增强,呈浓度依赖关系,差异有统计学意义(P<0.05)。结论1μmol/L紫杉醇配伍1/128 mg/ml比伐卢定相较于单纯应用紫杉醇,体外培养的HCASMC相对增殖活性进一步下降至75%左右,同时HCAEC增殖活性不受影响,二者合用体现了中药配伍增效减毒的作用,可为新型内皮友好型中药单体复合DCB的研发提供思路和依据。Objective To investigate the influence of paclitaxel-bivalirudin complex(Luofengning 0)on the proliferation of human coronary artery smooth muscle cells(HCASMC)and human coronary artery endothelial cells(HCAEC)cultured in vitro,and provide a basis for development of drug-coated balloon(DCB)of new generation of monomer complex of Chinese medicinal.Methods HCASMC and HCAEC were cultured in vitro and passed to 4-6 generations,and then divided into paclitaxel group(1μmol/L)and paclitaxel-bivalirudin group(PB group).PB group was treated with 1μmol/L paclitaxel combined with different concentrations of bivalirudin(1/256 mg/ml,1/128 mg/ml,1/64 mg/ml,1/32 mg/ml,1/16 mg/ml,1/8 mg/ml,1/4 mg/ml,1/2 mg/ml and 1 mg/ml).After 48 h,the proliferative activities of HCASMC and HCAEC were detected by using MTT for screening the optimum ratio of paclitaxel to bivalirudin,which inhibited HCASMC proliferation without affecting even promoting HCAEC proliferation.The purpose was to provided test data support for DCB of endotheliumfriendly monomer complex of Chinese medicinal.Results Compared with paclitaxel group,in PB group,paclitaxel combined with low-concentration bivalirudin(1/256 mg/ml)promoted the inhibitory effect of paclitaxel on HCASMC proliferation,and the effect increased with the increase of bivalirudin concentration,showing a concentration-dependent relationship(P<0.05).When paclitaxel combined with low-concentration bivalirudin(1/256 mg/ml and 1/128),it had no influence on HCAEC proliferation(P>0.05).When bivalirudin concentration was higher than 1/128 mg/ml,the inhibitory effect of paclitaxel on HCAEC proliferation was promoted in PB group compared with paclitaxel group,showing a concentration-dependent relationship(P<0.05).Conclusion Compared with paclitaxel alone,paclitaxel(1μmol/L)combined with bivalirudin(1/128 mg/ml)can reduce further the proliferative activity of HCASMC in vitro by about 75%,meanwhile the proliferative activity of HCAEC is not affected.Paclitaxel combined with bivalirudin showed the effects of in

关 键 词：紫杉醇 比伐卢定 人冠状动脉平滑肌细胞 人冠状动脉内皮细胞 增殖活性 

分 类 号：R543.3[医药卫生—心血管疾病]