摘要
目的:研究丙泊酚对苯肾上腺素(phenylephrine, PE)诱导H9C2心肌细胞的影响及机制。方法:H9C2细胞均分为5组,PE诱导细胞凋亡模型,用0.5,1,1.5 mmol·L^(-1)丙泊酚预处理。采用流式细胞术检测凋亡率;RT-qPCR检测GRP78/PERK/CHOP通路的mRNA表达;蛋白质印迹检测GRP78/PERK/CHOP通路蛋白、caspase-12、caspsae-3、SERCA2a的表达;定磷法检测SERCA2a活性。结果:PE诱导心肌细胞凋亡率升高,GRP78/PERK/CHOP通路mRNA及蛋白表达升高,caspase-12、caspsae-3表达升高,SERCA2a蛋白表达及活性降低,差异有统计学意义(P均<0.05)。中、高浓度的丙泊酚可明显逆转PE诱导的上述指标变化,且差异有统计学意义(P均<0.05)。结论:丙泊酚通过恢复SERCA2a的活性及表达量、抑制GRP78/PERK/CHOP通路,降低PE诱导的心肌细胞凋亡。
OBJECTIVE To investigate the effect and mechanism of propofol on phenylephrine(PE)-induced cardiomyocytes.METHODS H9C2 cells were divided into five groups, and PE-induced apoptosis models were pretreated with 0.5 mmol·L^(-1),1 mmol·L^(-1),and 1.5 mmol·L^(-1) concentrations of propofol.Apoptosis rate was detected by Flow Cytometry;mRNA expression of GRP78/PERK/CHOP pathway was detected by Quantitative Real-time PCR;expression of GRP78/PERK/CHOP pathway-related proteins, caspase-12,caspsae-3,SERCA2a was detected by western blotting;SERCA2a activity was detected by the phosphorus fixation.RESULTS PE induced increased apoptosis in cardiomyocytes, increased mRNA and protein expression of GRP78/PERK/CHOP pathway, increased expression of caspase-12 and caspsae-3,and decreased expression and activity of SERCA2a protein, and the differences were statistically significant(all P<0.05).Medium and high concentrations of propofol significantly reversed the PE-induced changes in the above indices, and the differences were statistically significant(all P<0.05).CONCLUSION Propofol reduces PE-induced cardiomyocytes apoptosis by restoring the activity and expression of SERCA2a and inhibiting the GRP78/PERK/CHOP pathway.
作者
冷孜璇
单正宜
刘荟婷
吕家磊
靳步
赵鹏
LENG Zi-xuan;SHAN Zheng-yi;LIU Hui-ting;LYU Jia-lei;JIN Bu;ZHAO Peng(Department of Forensic Medicine,School of Basic Medical Sciences,Qingdao University,Shandong Qingdao 266071,China;Department of Pathology,Affiliated Hospital of Qingdao University,Shandong Qingdao 266071,China;Department of Pathology,Jiading Branch of Shanghai First People's Hospital/Jiangqiao Hospital of Jiading District,Shanghai 201803,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第2期163-167,共5页
Chinese Journal of Hospital Pharmacy
基金
山东省自然科学基金面上项目(编号:ZR2021MH127)。
关键词
丙泊酚
H9C2
凋亡
内质网应激
propofol
H9C2
apoptosis
endoplasmic reticulum stress