不同降压药和他汀类药物对波动高糖诱导的人脐静脉内皮细胞凋亡及增殖的影响  

Effects of different antihypertensive drugs and statins on proliferation and apoptosis of human umbilical vein endothelial cells induced by intermittent high glucose

作　　者：林敏华[1] 陈子春[1] 富显果[2] 林宇涵[1] 许双临[1] 

机构地区：[1]福建医科大学附属宁德市医院临床药学室,福建宁德352100 [2]福建医科大学附属宁德市医院中心实验室,福建宁德352100

出　　处：《中华高血压杂志》2014年第10期952-957,共6页Chinese Journal of Hypertension

基　　金：福建省自然科学基金项目(2012J01436);福建省卫生厅青年科研课题(2011-1-45);宁德市科学技术计划项目(20110008)

摘　　要：目的探讨不同降压药物和他汀类药物对波动高糖诱导的人脐静脉内皮细胞(HUVEC)增殖及凋亡的影响。方法以体外培养的HUVEC为研究对象,分为以下几种处理:1不做任何处理(正常对照);2以5.5/30.5mmol/L波动高糖干预细胞,每24h交替更换一次(波动高糖);3分别以3种浓度(0.2、1.0、5.0μmol/L)的硝苯地平、缬沙坦、氟伐他汀、卡托普利先与细胞孵育1h后再加入波动高糖(5.5/30.5mmol/L)培养基,分别于干预后48、72、120和168h采用细胞计数试剂盒(CCK-8)检测细胞存活率和AnnexinⅤ-PI染色流式细胞仪法检测细胞早期凋亡率(波动高糖+药物)。结果早期凋亡率结果显示,除波动高糖+氟伐他汀[(22.6±11.2)%]外,波动高糖+硝苯地平[(7.5±3.9)%]、波动高糖+缬沙坦[(8.0±3.1)%]、波动高糖+卡托普利[(6.4±3.9)%]早期凋亡率低于波动高糖组[(13.1±5.9)%](均P<0.01);在波动高糖+氟伐他汀组中,随着药物剂量的加大,细胞早期凋亡率逐渐增大,其中大剂量组(5μmol/L)明显高于波动高糖组(P<0.01)。细胞存活率结果显示,除波动高糖+大剂量氟伐他汀组(0.38±0.25)外,波动高糖+硝苯地平(2.06±0.91)、波动高糖+缬沙坦(1.97±0.89)、波动高糖+卡托普利(1.56±0.72)、波动高糖+0.2μmol/L氟伐他汀(1.60±0.58)、波动高糖+1μmol/L氟伐他汀(1.49±0.70)组细胞存活率高于波动高糖组(1.00±0.35,均P<0.01)。细胞凋亡率与存活率多因素析因分析显示,干预方式与药物剂量、干预方式与干预时间之间存在交互作用(均P<0.01)。结论硝苯地平、卡托普利和缬沙坦3种药物可有效抑制波动高糖诱导的HUVEC凋亡并改善其增殖;大剂量氟伐他汀则促进其凋亡并抑制其增殖。Objective To investigate the effects of different antihypertensive drugs and statins on the proliferation and apoptosis of human umbilical vascular endothelial cells（HUVEC）induced by the intermittent high glucose.Methods HUVEC were treated as follows：1incubated without any interventions（control group）. 2 induced with intermittent high glucose（IHG,alternately cultured in glucose at a concentration of 5.5or 30.5 mmol/L for24hours）. 3pre-treated respectively with nifedipine,captopril,valsartan and fluvastatin at the three different concentrations（0.2,1.0and 5.0μmol/L）for one hour before IHG. After incubation for 48,72,120 and 168h respectively,the apoptosis of HUVEC was detected by AnnexinⅤ-PI apoptotic flow cytometric kit and the cell proliferation by CCK-8assay（IHG combined with drug intervention group）. Results The early apoptotic rate was significantly reduced by coadministration of IHG plus nifedipine[（7.5±3.9）%],valsartan[（8.0±3.1）%]or captopril[（6.4±3.9）%],as compared with that in IHG group[（13.1±5.9）%]. However,the apoptotic rate was elevated by IHG and fluvastatin co-incubation[（22.6±11.2）%],which rose gradually with the increase of fluvastatin dose,especially in the flushing dosage of 5μmol/L（P〈0.01）. Alternatively,the cell proliferation was increased by the combined treatment of IHG plus nifedipine（2.06±0.91）,valsartan（1.97±0.89）,captopril（1.56±0.72）,fluvastatin at the dose of 0.2（1.60±0.58）or 1μmol/L（1.49±0.70）,while it was decreased in the IHG plus 5μmol/L fluvastatin group[（0.38±0.25）%,P〈0.01]. There was interaction effect between drug interventions and dosages,as well as drug interventions and time following the multi-factor analysis of the apoptosis rates and cell proliferation rates. Conclusion Nifedipine,captopril and valsartan can inhibit the apoptosis of HUVEC induced by the intermittent high glucose and promote the proliferation,but the fluvastatin with flushing dose can promote the apoptosis and inhibit t

关 键 词：波动高糖 人脐静脉内皮细胞 凋亡 增殖 氟伐他汀 

分 类 号：R587.2[医药卫生—内分泌]