ZD7288抑制风湿性心瓣膜病变心房颤动患者右心耳心肌细胞HCN2表达  

ZD7288 inhibits the expression level of HCN2 in cardiomyocytes of atrial fibrillation complicated with rheumatic heart disease

作　　者：刘文洲[1] 孙宇[1] 梁飞海 赵文[1] 韦高翔[1] 邓海龙 钱俊[1] 冼磊[1] LIU Wenzhou;SUN Yu;LIANG Feihai;ZHAO Wen;WEI Gaoxiang;DENG Hailong;QIAN Jun;XIAN Lei(Department of Cardiothoracic Surgery,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530007,China)

机构地区：[1]广西医科大学第二附属医院心胸外科,南宁530007

出　　处：《国际心血管病杂志》2022年第3期181-185,共5页International Journal of Cardiovascular Disease

基　　金：广西医科大学青年科学基金(GXMUYSF201801)。

摘　　要：目的:观察ZD7288抑制超极化激活环核苷酸调控通道基因家族-2(HCN2)在风湿性心瓣膜病变心房颤动(房颤)患者右心耳组织中的作用。方法:收集43例风湿性心瓣膜病变患者右心耳组织,分为窦性心律患者(SR组)、心房颤动组(AF组)、ZD7288(10μmol/L)干预房颤组(Z1组)和ZD7288(50μmol/L)干预房颤组(Z2组);采用全细胞膜片钳技术记录If电流密度,荧光定量聚合酶链反应及Western blot检测右心耳组织心肌细胞中HCN2表达水平。结果:相同激活电位时,AF组心肌细胞If电流密度明显大于SR组、Z1组和Z2组,且随电位增加激活更快,尤其在-70 mV时,AF组电流密度明显高于SR组、Z1组和Z2组,分别为(48.36±1.05)pA/pF、(31.03±1.17)pA/pF、(31.12±1.48)pA/pF和(30.32±1.33)pA/pF(P<0.01)。荧光定量聚合酶链反应结果显示AF组、SR组、Z1组和Z2组HCN2 mRNA表达水平分别为1.60±0.36、0.24±0.02、0.28±0.02和0.25±0.03;Western blot结果显示AF组、SR组、Z1组和Z2组HCN2蛋白表达量分别为0.95±0.21、0.22±0.08、0.27±0.07和0.23±0.08;AF组HCN2 mRNA和蛋白表达水平均明显高于SR组、Z1组和Z2组(P均<0.01)。结论:HCN2参与风湿性心瓣膜病患者房颤的发生发展过程,而ZD7288可抑制HCN2的表达。Ojective:To find out the expression level of HCN2 inhibited by ZD7288 in atrial fibrillation(AF)patients with rheumatic heart disease(RHD).Methods:A total of 43 patients with RHD were divided into 4 groups,sinus rhythm(SR)group,AF group,Z1 group(intervene at AF by 10μM ZD7288)and Z2 group(intervene at AF by 50μM ZD7288).The If density was measured by a whole-cell patch clamp technique.The expression of HCN2 was detected by FQ-PCR and western blotting.Results:Compared SR group,Z1 group and Z2 group,If density in single myocyte was significantly increased in AF group under same activate potential,and the activation was faster with the increase of the potential.Especially at-70 mV,the current density of the AF group was significantly higher than that of the other three groups[(48.36±1.05)pA/pF,(31.03±1.17)pA/pF,(31.12±1.48)pA/pF,and(30.32±1.33)pA/pF,P<0.01].The results of FQ-PCR showed that the expressions levels of HCN2 mRNA in AF group,SR group,Z1 group and Z2 group were 1.60±0.36,0.24±0.02,0.28±0.02 and 0.25±0.03.The results of western blotting showed the expressions levels of HCN2 in AF group,SR gruop,Z1 group and Z2 group were 0.95±0.21,0.22±0.08,0.27±0.07 and 0.23±0.08.The expressions levels of HCN2 in AF group were higher than the other groups(all P<0.01).Conclusion:The high expression level of HCN2 play an important role in AF in the patients with RHD,and ZD7288 can inhibit the expression levels of HCN2.

关 键 词：风湿性心脏瓣膜病 心房颤动 ZD7288 超极化激活环核苷酸调控通道基因家族-2 

分 类 号：R541.75[医药卫生—心血管疾病] R541.2[医药卫生—内科学]