哌唑嗪对去甲肾上腺素诱导心肌细胞凋亡的影响

目的：研究α受体拮抗剂哌唑嗪对去甲肾上腺素诱导的原代培养心肌细胞凋亡的影响。方法：采用噻唑蓝（MTT）法分析原代培养心肌细胞存活率；乳酸脱氢酶（LDH）外漏实验和吉姆萨染色实验观察原代心肌细胞损伤；JC-1免疫荧光实验检测线粒体膜电位变化；Annexin V-FITC/PI双染，流式细胞仪检测细胞凋亡。结果：NE（100 μmol·L^-1）作用于原代培养心肌细胞48 h，细胞存活率降低；LDH外漏增加；细胞形态改变，细胞数减少、胞体膨大、胞核居中、胞间间隙增大，呈明显病理学特征；线粒体膜电位降低；心肌细胞凋亡率增加。哌唑嗪明显改善去甲肾上腺素诱导的原代培养心肌细胞损伤，增加MTT值、降低LDH外漏量、改善心肌细胞病理形态、增加心肌细胞线粒体膜电位、降低心肌细胞凋亡率（P<0.05或P<0.01）。结论：哌唑嗪能显著抑制去甲肾上腺素诱导的心肌细胞凋亡，本实验为α受体阻断剂改善高交感诱导心肌细胞凋亡提供实验基础与理论指导。

Inhibitory effects of prazosin on apoptosis of primary cultured cardiac myocytes induced by norepinephrine in vitro

OBJECTIVE To investigate the inhibitory effect of α-receptor antagonist (prazosin) on norepinephrine induced apoptosis of primary cultured cardiac myocytes in vitro.METHODS The survival rate of cardiac myocytes induced by norepinephrine was assayed by using tetrazolium salt (MTT) colorimetric assay and the cell injury was detected by lactate dehydrogenase (LDH) assay in medium.Cell morphology was checked with Giemsa staining.JC-1 fluorescence staining was used to measure the mitochondrial membrane potential.The apoptotic rate was determined by flow cytometry.RESULTS After exposure NE (100 μmol · L^-1) to cardiac myocytes for 48 h,the cell viability was decreased and LDH leakage in medium increased.The cell morphology was changed with pathological characteristics,and the mitochondrial membrane potential was decreased,the apoptosis rate was increased (P<0.05 or P<0.01).Pretreatment with prazosin could significantly ameliorate the damage and apoptotic rate of primary cardiomyocytes induced by norepinephrine.CONCLUSION Prazosin can inhibit norepinephrine induced cardiomyocyte apoptosis,which suggests that α-receptor blocker can alleviate the cardiomyocyte apoptosis induced by high sympathetic activity in clinical practice,and provide a guideline and experimental basis in clinical practice.