川芎嗪通过调控组蛋白乙酰化修饰上调SERCA2a对心力衰竭小鼠模型的防治机制研究  

Research on Prevention and Control Mechanism of the Ligustrazine Up Regulates SERCA2a by Regulating Histone Acetylation in A Mouse Model of Heart Failure

作　　者：杨英 张文华 丁铭 吴翔 YANG Ying;ZHANG Wen-hua;DING Ming;WU Xiang(Department of Critical Medicine,the Fourth People’s Hospital of Shaanxi,Xi’an 710043,China;School of Basic Medicine,School of Medicine,Xi’an Jiaotong University,Xi’an 710012,China)

机构地区：[1]陕西省第四人民医院重症医学科,西安710043 [2]西安交通大学医学院基础医学院,西安710012

出　　处：《现代检验医学杂志》2021年第6期34-40,共7页Journal of Modern Laboratory Medicine

摘　　要：目的研究川芎嗪(ligustrazine,LGSZ)是否通过调控组蛋白乙酰化修饰上调心肌肌浆网Ca^(2+)-ATPase 2a(SERCA2a)在预防心力衰竭中发挥作用。方法通过微创性横向主动脉缩窄(TAC)手术构建心力衰竭的小鼠模型,超声心动图评价LGSZ干预后心脏功能变化,实时定量聚合酶链式反应(qPCR),western blot及ChIp检测SERCA2a相关蛋白和基因表达,并通过试剂盒检测组蛋白去乙酰化酶1(HDAC1)活性。结果TAC+LGSZ组手术前后左心室前壁舒张末期厚度(LVAWd)、舒张末期左室后壁厚度(LVPWd)、射血分数(EF)及缩短分数(FS)比较,差异均无统计学意义(t=0.245~1.054,均P>0.05)。TAC+LGSZ组SERCA2a mRNA和SERCA2a蛋白表达显著高于TAC组,差异有统计学意义(t=4.817,3.913,均P<0.001)。TAC+LGSZ组中总AcH3和AcH3K9与SHAM组比较,差异无统计学意义(t=0.624,1.249,均P>0.05)。TAC组HDAC1酶活性和HDAC1水平均高于SHAM组和TAC+LGSZ组,差异均有统计学意义(t=2.361~4.309,均P<0.05)。TAC组心脏组织中,Atp2a2启动子区域附近GATA4和Mef2c水平低于TAC+LGSZ组,差异有统计学意义(t=4.816,5.007,均P<0.001)。结论LGSZ通过调控组蛋白乙酰化修饰上调SERCA2a在压力超负荷引起的心力衰竭中起预防作用。Objective To study the ligustrazine(LGSZ)whether upregulates sarcoplasmic reticulum Ca2+-ATPase(SERCA2a)by regulating histone acetylation to play a role in preventing heart failure.Methods Minimally invasive transverse aortic constriction(TAC)surgery was used to construct a mouse model of heart failure.Echocardiography was used to evaluate the change of cardiac function after LGSZ intervention.The real time quantitative polymerase chain reaction(qPCR),Western blot and ChIp were used to detect the expression of SERCA2a related protein and gene,and the HDAC1 activity was detected by kit.Results There were no significant difference in left ventricular posterior wall thickness(LVAWd),left ventricular posterior wall thickness(LVPWd),ejection fraction(EF)and fractional shortening(FS)before and after operation in TAC+LGSZ group(t=0.245,1.054,all P>0.05).The expression of SERCA2a mRNA and protein in TAC+LGSZ group were significantly higher than those in TAC group(t=4.817,3.913,all P<0.001).There were no significant difference in total AcH3 and AcH3k9 between TAC+LGSZ group and SHAM group(t=0.624,1.249,P=0.540,0.228).The HDAC1 enzyme activity and HDAC1 level in TAC group were higher than those in SHAM group and TAC+LGSZ group(t=2.361~4.309,all P<0.05).The levels of GATA4 and Mef2c near Atp2a2 promoter region in TAC group were lower than those in TAC+LGSZ group(t=4.816,5.007,all P<0.001).Conclusion LGSZ up-regulates SERCA2a by regulating histone acetylation to prevent heart failure caused by pressure overload.

关 键 词：川芎嗪 组蛋白乙酰化 心肌肌浆网Ca^(2+)-ATPase 2a 心力衰竭 

分 类 号：R-332[医药卫生]