雷诺嗪对缺氧/复氧诱导的H9c2心肌细胞损伤的保护作用  

The protective effect of ranolazine on H9c2 cardiomyocyte injury induced by hypoxia/reoxygenation

作　　者：郭峰[1] 蒋广恩[1] 林军[1] GUO Feng;JIANG Guang-en;LIN Jun(Care Ward,Zhongshan Hospital Affiliated to Xiamen University,Xiamen 361000,Fuyjian Province,China)

机构地区：[1]厦门大学附属中山医院保健病房,福建厦门361000

出　　处：《中国临床药理学杂志》2022年第16期1873-1876,共4页The Chinese Journal of Clinical Pharmacology

基　　金：福建省自然科学基金资助项目(2014J01438)。

摘　　要：目的探讨雷诺嗪对缺氧/复氧(H/R)诱导的H9c2心肌细胞损伤的保护作用。方法将H9c2心肌细胞放置于氧浓度为3%的培养箱中培养4 h后,再放置在氧浓度为21%的培养箱中培养4 h,以构建H9c2心肌细胞H/R损伤模型。将H9c2心肌细胞随机分为空白组、模型组、低剂量实验组和高剂量实验组。除空白组外,其余各组均构建H/R损伤模型。低剂量及高剂量实验组分别加入5和10μg·mL^(-1)雷诺嗪,空白组及模型组分别加入等体积生理盐水。以Annexin V-FITC/PI法检测细胞凋亡率;以酶联免疫吸附试验(ELISA)检测细胞培养基中乳酸脱氢酶(LDH)的表达水平;以实时聚合酶链反应(RT-PCR)测定细胞中Bcl-2相关X蛋白(Bax)、凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)mRNA的表达水平。结果模型组、低剂量、高剂量实验组及空白组细胞凋亡率分别为(69.54±8.67)%,(42.11±10.03)%,(33.78±9.54)%和(4.17±1.34)%;这4组的LDH分别为(121.38±30.41),(97.64±19.27),(81.28±17.34)和(40.32±6.59)ng·mL^(-1);这4组的Bax mRNA表达水平分别为3.48±0.53,3.01±0.42,2.56±0.38和0.93±0.17;这4组的Bcl-2 mRNA表达水平分别为0.53±0.28,0.70±0.27,0.82±0.39和1.18±0.42;这4组的Caspase-3 mRNA表达水平分别为1.68±0.33,1.52±0.27,1.22±0.30和0.96±0.21。上述指标,模型组与空白组比较,低、高剂量实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论雷诺嗪对缺氧-复氧诱导的H9c2心肌细胞损伤发挥保护作用,可能与调节凋亡蛋白表达有关。Objective To investigate the protective effect of ranolazine on H9c2 cardiomyocyte injury induced by hypoxia/reoxygenation(H/R).Methods H9c2 cardiomyocytes were cultured in an oxygen concentration of 3%for 4 h and then cultured again in an oxygen concentration of 21% for 4 h.H9c2 cardiomyocytes were divided into blank group,model group,experimental-L group and experimental-H group.All of them were processed to construct H/R model excepted blank group.Experimental-L and experimental-H group were added with 5 and 10μg·m L^(-1)ranolazine,respectively;while blank group and model group were added with equal volume of saline.The apoptosis rates were detected by using Annexin V-FITC/PI,and level of lactate dehydroxgenase(LDH)of cell were detected by using enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of Bcl-2 related X protein(Bax),apoptosis-related protein B-cell lymphoma/leukemia-2(Bcl-2)and Caspase-3 in cells were determined by using real-time polymerase chain reaction(RT-PCR).Results The apoptosis rates in model group,experimental-L group,experimental-H group and blank group were(69.54±8.67)%,(42.11±10.03)%,(33.78±9.54)% and(4.17±1.34)%;the level of LDH in four groups were(121.38±30.41),(97.64±19.27),(81.28±17.34)and(40.32±6.59)ng·m L^(-1);Bax mRNA in four groups were 3.48±0.53,3.01±0.42,2.56±0.38 and 0.93±0.17;Bcl-2 mRNA in four groups were 0.53±0.28,0.70±0.27,0.82±0.39 and 1.18±0.42;Caspase-3 mRNA in four groups were 1.68±0.33,1.52±0.27,1.22±0.30 and 0.96±0.21.The differences in the above indicators between model group and blank group,or between experimental-L group,experimental-H group and model group were statistically significant(all P<0.05).Conclusion Ranolazine had a protective effect on H9c2 cardiomyocyte injury induced by H/R by regulating expression of apoptosis protein.

关 键 词：雷诺嗪 缺氧/复氧 H9C2心肌细胞 凋亡蛋白 

分 类 号：R96[医药卫生—药理学]