乌头提取物通过调控蛋白激酶C信号通路对心力衰竭大鼠钙转运及心肌线粒体呼吸功能的影响  

Effects of Aconitum carmichaelii Extract on Calcium Transport and Myocardial Mitochondrial Respiratory Function in Rats with Heart Failure by Regulating PKC Signaling Pathway

作　　者：郑曦 陈世蓉 熊挺淋 王德伟 王浩宇 ZHENG Xi;CHEN Shi-rong;XIONG Ting-lin;WANG De-wei;WANG Hao-yu(Deartment of Cardiovascular Medicine,Nanchong Central Hospital,Nanchong Sichuan 637000)

机构地区：[1]南充市中心医院心血管内科,四川南充637000

出　　处：《世界中西医结合杂志》2023年第1期62-67,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：2020南充市市校科技战略合作项目(20SXQT0197)。

摘　　要：目的探究乌头提取物通过调控蛋白激酶C(Protein kinase C,PKC)信号通路对心力衰竭大鼠钙转运及心肌线粒体呼吸功能的影响。方法将30只雄性SD大鼠随机分为3组,假手术组9只、模型组9只和药物组9只(假手术组大鼠造模时死亡1只,造模组造模失败1只,死亡1只)。根据人临床应用剂量及大鼠换算系数折算给药剂量,药物组大鼠灌胃乌头提取液0.04 mg/kg,其余两组大鼠均灌胃等量的生理盐水干预。均连续干预28 d后,观察比较3组大鼠心功能指标[左心室收缩压(Left ventricular systolic pressure,LVSP),左心室舒张末压(Left ventricular end diastolic pressure,LVEDP);左室内压上升最大速率(LV+dp/dt_(max));左室内压下降最大速率(LV-dp/dt_(max))];RT-PCR检测心肌细胞中DAG-β、PKC-εmRNA和心肌组织中钙转运蛋白mRNA表达;检测线粒体呼吸功能;蛋白质印迹检测线粒体呼吸链复合酶Ⅰ~Ⅴ的蛋白表达。结果模型组大鼠LVSP、LV+dp/dt_(max)、LV-dp/dt_(max)及心肌钙转运蛋白RyR2、SERCA2A mRNA表达较假手术组降低,LVEDP及DAG-β、PKC-εmRNA表达较假手术组升高,差异有统计学意义(P<0.05);药物组大鼠LVSP、LV+dp/dt_(max)、LV-dp/dtma及心肌钙转运蛋白RyR2、SERCA2A mRNA表达高于模型组,LVEDP及DAG-β、PKC-εmRNA表达较模型组低,差异有统计学意义(P<0.05)。模型组大鼠态3呼吸、最大呼吸、RCR1、RCR2值及线粒体呼吸链复合酶Ⅲ、Ⅳ表达较假手术组均降低,态4呼吸较假手术组升高,差异有统计学意义(P<0.05);模型组比较,药物组大鼠态3呼吸、最大呼吸、RCR1、RCR2值及线粒体呼吸链复合酶Ⅲ、Ⅳ表达均升高,态4呼吸降低,差异有统计学意义(P<0.05)。结论乌头提取物能抑制PCK信号通路的激活,修复心室细胞钙转运,改善线粒体呼吸功能,进而修复心衰。Objective To investigate the effects of Aconitum carmichaelii extract(ACE)on calcium transport and myocardial mitochondrial respiratory function in rats with heart failure by regulating protein kinase C(PKC)signaling pathway.Methods Thirty male SD rats were randomly divided into a sham operation group(n=9),a model group(n=9),and a drug intervention group(n=9).One rat in the sham operation group died during modeling,and in the model group,one rat failed to be modeled and one rat died.The dosage was converted according to human clinical dosage and rat conversion factor.The rats in the drug intervention group were intragastrically administered with ACE at 0.04 mg/kg,and those in the other two groups were with the same amount of normal saline.After continuous intervention for 28 days,the cardiac function indexes of the three groups were observed and compared.The mRNA expression of DAG-βand PKC-εin myocardial cells and calcium transporter in myocardial tissues was detected by RT-PCR.Mitochondrial respiratory function was detected.Western blot was used to detect the protein expression of mitochondrial respiratory chain complexesⅠ~Ⅴ.Results The mRNA expression of LVSP,LV+dp/dt_(max),LV-dp/dt_(max),and cardiac calcium transporters RyR2 and SERCA2A in the model group was lower than that in the sham operation group,and the mRNA expression of LVEDP,DAG-β,and PKC-εwas higher than that in the sham operation group(P<0.05).The mRNA expression of LVSP,LV+dp/dt_(max),LV-dp/dt_(max),and cardiac calcium transporters RyR2 and SERCA2A in the drug intervention group was higher than that in the model group,and the mRNA expression of LVEDP,DAG-β,and PKC-εwas lower than that in the model group(P<0.05).The stateⅢrespiration,maximal respiration,RCR1 value,RCR2 value,and the expression of mitochondrial respiratory chain complexesⅢandⅣin the model group were lower than those in the sham operation group,and the stateⅣrespiration was higher than that in the sham operation group(P<0.05).Compared with the model group,the drug i

关 键 词：乌头提取物 PKC信号通路 心力衰竭 钙转运 心肌线粒体呼吸功能 

分 类 号：R285.5[医药卫生—中药学]