摘要
目的探讨瑞舒伐他汀钙对尼古丁诱导人脐静脉内皮细胞(HUVEC)基质金属蛋白酶2(MMP2)表达的影响。方法取健康剖腹产孕妇的HUVEC进行培养,选择2~4代细胞进行实验(n=5)。分别采用不同浓度(0、1、10、100/μmol/L)尼古丁进行24h处理以及采用100μmol/L尼古丁进行不同时间(0、6、12、24、48h)处理,处理后细胞进行半定量RT-PCR,Western blot检测MMP-2mRNA及蛋白的表达(n=5);内皮细胞首先用系列浓度(2,4,7,10/μg/L)瑞舒伐他汀钙进行预孵育12h,然后对药物干预后细胞进行100μmol/L尼古丁处理24h(n=50)。结果尼古丁呈浓度及时间依赖性诱导HuVEc中MMP-2表达:MMP2表达随尼古丁浓度增加而升高;尼古丁诱导MMP2表达随时间延长而增加。瑞舒伐他汀钙可浓度依赖性地抑制尼古丁诱导的MMP-2的表达[mRNA水平:2、4、7、10μg/L抑制率分别为8.6%、42.5%、66.9%、80.3%,均P〈0.05;蛋白水平:2、4、7、10μg/L抑制率分别为10.6%、37.6%、74.1%、88.2%,均P〈0.051。结论尼古丁是诱导HUVEC中MMP表达的重要因素;瑞舒伐他汀钙能够抑制该进程,且具有剂量依赖性。
Objective To explore the effect of rosuvastatin on the expression of matrix metalloproteinase-2(MMP2 ) in human umbilical vein endothelial cells (HUVEC) induced by nicotine. Methods HUVEC were isolated from umbilical cords of healthy caesarean women and cells at passages 2-4 were used in this study (n= 5). Cells were treated with different concentration of nicotine (0, 1, 10, 100 μmol/L) for 24 h or treatd with 100 μmol/L for different time (0, 6, 12, 24, 48 h), and then the expression of MMP-2 mRNA and protein in cells of the two groups were detected using semiquantitative real time PCR and Western blot ( n=5). Cells were incubated in series concentration rosuvastatin calcium (2, 4, 7, 10 μg/L) for 12 h, and then the incubated cells were treated with 100 μmol/L nicotine for 24 h after pharmacologic interventions (n 5). Results HUVEC MMP 2 expression was induced by nicotine in a concentration-dependent and time-dependent manner. The expression of MMP-2 induced by nicotine was inhibited by rosuvastatin calcium in a concentration-dependent [on mRNA level: the inhibition rates of 2, 4, 7, 10 μg/L were 8.6%, 42.5%, 66.9% and 80.3% respectively, all P〈0.05; on protein level: the inhibition rates of 2, 4, 7, 10μg/L were 10. 6%, 37.6%, 74.1%, 88.2% respectively, all P.〈0. 05]. Conclusion Nicotine is a major factor which can induce the expression of MMP-2 in HUVEC, which is a dangerous pathogenic factor in smoking. Rosuvastatin calcium can inhibit the process in a dose dependent manner.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2013年第11期1066-1070,共5页
Chinese Journal of Hypertension
关键词
尼古丁
脐静脉内皮细胞
基质金属蛋白酶
瑞舒伐他汀钙
Nicotine
Human umbilical vein endothelial cells
Matrix metalloproteinase
Rosuvastatin calcium