马来酸依那普利叶酸片联合阿托伐他汀对大鼠主动脉平滑肌细胞内质网应激的影响  

Effects of enalapril maleate folate tablets combined with atorvastatin on endoplasmic reticulum stress in rat aortic smooth muscle cells

作　　者：黄剑锋[1] 肖善花 黄绍烈[1] 赵宇[2] 江小杰 熊玲兵 周爱云[1] 陈莉[1] 霍勇[5] 钟伟兵 张必龙 邱宇安 胡永辉[8] 左汉恒[9] 龚春[10] HUANG Jian-feng;XIAO Shan-hua;HUANG Shao-lie;ZHAO Yu;JIANG Xiao-jie;XIONG Ling-bing;ZHOU Ai-yun;CHEN Li;HUO Yong;ZHONG Wei-bing;ZHANG Bi-long;QIU Yu-an;HU Yong-hui;ZUO Han-heng;GONG Chun(Deparmenl of Vitrasonic Diagnosis,The First Affiliated Hospital of Nanchang University,Nanchang 330006,Jiangxi Province,China;Department of Cardurvascular Medicine,The Fourth Affiliated Hospital of Nanchang Universily,Nanchang 330006,Jitingxi Province,China;Department of Cardimxiscular Medicine,The Third Affiliated Hospital of Nanchang University,Manchang 330006,Jiangxi Province,China;Department of Cardiovascular Medicine,Nanchang Third Hospital,Nanchang 330006,Jiangxi Province,China;DeparmerU of Ultrasonic Diagnosis,Beijing University First Hospital,Beijing 100034,China;Deparmenl of Uilrasorw Diagnosis,Ganzhou Municipal Hospital,Ganzhou 341000,Jiangxi Province,China;DeparmerU of Ultrasonic Diagnosis,Jiangxi Second People's Hospital,Nanchang 330006,Jiangxi Province,China;Deparmert of Vitrasonic Diagnosis,Tai'an Hospilal of Traditional Chinese Medicine,Tai'an 271000,Shandong Province,China;Department of Cardiovascular Medicine,Affiliated Hospital of Jining Medical Universily.Jining 272000,Shandong Province,China;Deparlmenl of Cardiovascular Medicine,Changzhou Wujin People's Hospilal,Changzhou 213000,Jiangsu Province,China)

机构地区：[1]南昌大学第一附属医院超声诊断科,江西南昌330006 [2]南昌大学第四附属医院心血管内科,江西南昌330006 [3]南昌大学第三附属医院,心血管内科,江西南昌330006 [4]南昌市第三医院心血管内科,南昌330006 [5]北京大学第一医院心血管内科,北京100034 [6]赣州市立医院心血管内科,江西赣州341000 [7]江西省第二人民医院心血管内科,江西南昌330006 [8]泰安市中医医院心血管内科,山东泰安271000 [9]山东济宁医学院附属医院心血管内科,山东济宁272000 [10]江苏常州市武进人民医院心血管内科,江苏常州213000

出　　处：《中国临床药理学杂志》2022年第4期338-341,351,共5页The Chinese Journal of Clinical Pharmacology

基　　金：江西省科技厅重点基金资助项目(S2017YBYFE0196)。

摘　　要：目的研究马来酸依那普利叶酸片联合阿托伐他汀对蛋氨酸诱导大鼠主动脉平滑肌细胞内质网应激(ERS)的影响。方法通过蛋氨酸诱导大鼠主动脉平滑肌细胞增殖,用马来酸依那普利叶酸片和阿托伐他汀单独或者联合孵育细胞12h,用MTT法筛选药物处理浓度。实验分为对照组(正常培养细胞)、模型组(蛋氨酸3.2 mmol·L-1)、依叶片组(蛋氨酸3.2 mmol·L-1+10μg·mL^(-1)马来酸依那普利叶酸片)、依叶片+阿托伐他汀组(蛋氨酸3.2 mmol·L-1+10μg·mL^(-1)马来酸依那普利叶酸片+5μg·mL^(-1)阿托伐他汀)。用荧光定量聚合酶链反应(PCR)和免疫荧光检测各组葡萄糖调节蛋白94(GRP94)、胱天蛋白酶12(caspase-12)和葡萄糖调节蛋白78(GRP78)表达。结果通过MTT筛选药物处理浓度,蛋氨酸颗粒浓度为3.2 mmol·L-1,阿托伐他汀和马来酸依那普利叶酸片浓度分别选择5μg·mL^(-1)和10μg·mL^(-1)。对照组GRP94、caspase-12和GRP78 mRNA表达分别为1.00±0.00,1.00±0.00,1.00±0.00,模型组分别为2.94±0.30,6.13±1.39和4.23±0.70,依叶片组分别为1.70±0.07,4.12±0.94和2.58±0.17,依叶片+阿托伐他汀组分别为1.24±0.07,3.20±0.22和1.70±0.06。与对照组相比,模型组的GRP94、caspase-12和GRP78 mRNA表达明显升高;与模型组相比,依叶片组和依叶片+阿托伐他汀组的GRP94、caspase-12和GRP78表达明显下降,差异均有统计学意义(均P <0.05)。免疫荧光结果表明依叶片组和依叶片+阿托伐他汀组中caspase-12和GRP94的表达水平显著低于模型组。结论蛋氨酸可能通过内质网应激途径参与并加重高血压引起的血管平滑肌重构的过程;马来酸依那普利叶酸片和阿托伐他汀处理后能够通过抑制内质网应激保护血管平滑肌细胞。Objective To investigate the effects of enalapril maleate folate tablets( EFA) combined with atorvastatin on endoplasmic reticulum stress( ERS) induced by methionine in rat aortic smooth muscle cells. Methods The proliferation of rat aorta smooth muscle cells was induced by methionine. The cells were incubated with enalapril maleate folate tablets and tongxinluo alone or in combination for 12 h,and the concentration was screened by MTT method. The experiment was divided into control group( normal cultured cells), model group( methionine 3. 2 mmol·L-1),EFA group( methionine 3. 2 mmol·L-1+10 μg · mL^(-1)enalapril maleate folate tablet), EFA + atorvastatin group( methionine 3. 2 mmol·L-1+ 10 μg·mL^(-1)enalapril maleate folate tablets + 5 μg·mL^(-1)atorvastatin). The expressions of gluconomodulin 94( GRP94),caspase-12( GRP78) and gluconomodulin 78( GRP78) were detected by fluorescence quantitative polymerase chain reaction( PCR) and immunofluorescence. Results The concentration of methionine was 3. 2 mmol·L-1 by MTT,5 μg·mL^(-1)and 10 μg·mL^(-1)by atorvastatin and enalapril maleate folate tablet concentration were selected,respectively. Expression of GRP94,caspase-12 and GRP78 mRNA in control group were 1. 00 ± 0. 00,1. 00 ± 0. 00,1. 00 ± 0. 00,which in model group were 2. 94 ± 0. 30,6. 13 ± 1. 39 and4. 23 ± 0. 70,which in EFA group were 1. 70 ± 0. 07,4. 12 ± 0. 94 and 2. 58 ± 0. 17,which in EFA + atorvastatin group were 1. 24 ± 0. 07,3. 20 ± 0. 22 and 1. 70 ± 0. 06,respectively. Compared with control group,GRP94,caspase-12 and GRP78 mRNA expressions in model group were significantly increased;compared with model group,the expressions of GRP94,caspase-12 and GRP78 mRNA were significantly decreased in EFA group and EFA +atorvastatin group( all P < 0. 05). The results of immunofluorescence showed that the expression levels of caspase-12 and GRP94 were significantly lower in EFA group and EFA + atorvastatin group than in model group. Conclusion Methionine may participate in and aggravate the re

关 键 词：马来酸依那普利叶酸片 阿托伐他汀 蛋氨酸 内质网应激 主动脉平滑肌细胞 

分 类 号：R972[医药卫生—药品]