阿托伐他汀对ox-LDL诱导的人脐静脉内皮细胞缝隙连接的影响  

Effects of Atorvastatin on Gap Junction of Human Umbilical Vein Endothelial Cells Induced by ox-LDL

作　　者：张秀梅[1] 于晓玲[1] 申玉超[1] 骆振华[2] 

机构地区：[1]辽宁医学院附属第一医院老年医学科,辽宁锦州121001 [2]辽宁医学院附属第一医院普外科,辽宁锦州121001

出　　处：《中国药房》2013年第5期412-415,共4页China Pharmacy

摘　　要：目的:研究阿托伐他汀对氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)连接蛋白(Connexin)43、Connexin40表达的影响。方法:将体外培养的HUVECs分为对照组、ox-LDL组、阳性对照组和阿托伐他汀组,除对照组外,其余组分别先在培养液、加入50μmol/L庚醇的培养液、加入不同剂量(0.01、0.1、1.0、10μmol/L)阿托伐他汀的培养液中处理30min,再分别加入50mg/L的ox-LDL继续培养24h。采用硝酸还原酶法测定各组NO浓度,免疫细胞化学法测定Connexin43蛋白定位表达,蛋白印迹法检测Connexin43、Connexin40蛋白定量表达。结果:与对照组比较,其余各组NO浓度均明显减少、Connexin43和Connexin40蛋白定量表达均明显增加(P均<0.01),其中除阳性对照组和10μmol/L阿托伐他汀组外,剩余各组均有Connexin43蛋白定位表达。与ox-LDL组比较,阳性对照组NO浓度明显增加、Connexin43和Connexin40蛋白定量表达明显减少(P<0.05或P<0.01),阿托伐他汀组随剂量增加NO浓度逐渐增加、Connexin43和Connexin40蛋白定量表达逐渐减少(P<0.05或P<0.01)。与阳性对照组比较,10μmol/L阿托伐他汀组上述指标均无统计学差异(P>0.05)。结论:阿托伐他汀呈剂量依赖性抑制ox-LDL诱导的HUVECs中Connexin43、Connexin40蛋白的增加,保护内皮间缝隙连接,从而发挥他汀类药物调脂外的抗动脉粥样硬化作用。OBJECTIVE： To investigate the effects of atorvastatin on the expression of Connexin 43 and Connexin 40 in human umbilical vein endothelial cells （HUVECs） induced by oxidized low-density lipoprotein （ox-LDL）. METHODS： Cultured HU- VECs were divided into control group, ox-LDL group, positive control group and atorvastatin groups. Except for control group, the other groups were treated with culture medium, culture medium （added 50 μmol/L heptanol）, culture medium （added 0.01, 0.1, 1.0 and 10 μmol/L atorvastatin） for 30 min, respectively, and then incubated with 50 mg/L ox-LDL for 24 h. NO concentra- tion was determined by nitrate reductase method, and location expression of Connexin 43 was observed using immunocytochemis- try, and quantitative expressions of Connexin 43 and Connexin 40 were measured by Western blotting. RESULTS： Compared with control group, NO concentration of other groups decreased significantly while expression of Connexin 43 and Connexin 40 in- creased significantly （P〈0.01）. The location expression of Connexin 43 was found in those groups except for positive control group and 10 μmol/L atorvastatin group. Compared with ox-LDL group, the NO concentration of positive control group increased significantly while the quantitative expression of Connexin 43 and Connexin 40 decreased significantly （P〈0.05 or P〈0.01）; NO concentration of atorvastatin groups increased and the quantitative expression of Connexin 43 and Connexin 40 decreased gradually in dose-dependent manner （P〈0.05 or P〈0.01）. Compared with positive control group, the above index of 10 μmol/L atorvastatin group had no statistical difference （P〉0.05）. CONCLUSIONS： Atorvastatin can obviously inhibit the protein expression of Con- nexin 43 and Counexin 40 in HUVECs injured by ox-LDL in dose-dependant manner and protect the gap junction of HUVECs to play lipid regulation and anti-atherosclerosis function of statins.

关 键 词：阿托伐他汀 人脐静脉内皮细胞 连接蛋白43 连接蛋白40 氧化型低密度脂蛋白 

分 类 号：R965[医药卫生—药理学]