Zhou Chen, Liu Qun, Xin Juan-Juan, Zhao Yu-Xue, Chen An-Li, Lu Feng-Yan, Zhang Wen-Xi, Gao Jun-Hong, Yu Xiao-Chun
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Science, Beijing 100700, China.
Third Clinical Medical College of Zhejiang Chinese Medical University.
Zhongguo Zhen Jiu. 2021 Sep 12;41(9):1029-35. doi: 10.13703/j.0255-2930.20200729-k0001.
To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca-ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure.
Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 μg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dt) were detected and arrhythmia types were observed and scored. SERCA2a protein and PLB protein expressions in left ventricular myocardial tissue of rats were detected by multiplex fluorescence Western blot.
Compared with the control group, LVSP and ±dp/dt all were decreased after modeling and at each time point after intervention in the model group (<0.01). Compared with the model group, ±dp/dt was increased in the aconitine group and the EA group at 1 min after intervention (<0.01, <0.05), +dp/dt was increased at 10 to 60 min after intervention in the aconitine group and at 20 to 60 min after intervention in the EA group (<0.01, <0.05), LVSP was increased at 1 min after intervention in the EA group (<0.01), while LVSP and ±dp/dt were all increased at 1 to 60 min after intervention in the EA plus aconitine group (<0.01, <0.05). Compared with the aconitine group, LVSP and +dp/dt were increased at 1 min after intervention in the EA group (<0.01, <0.05), LVSP and ±dp/dt at 1 min after intervention while +dp/dt at 20 to 60 min after intervention were all increased in the EA plus aconitine group (<0.01, <0.05). Compared with the EA group, +dp/dt was higher at 10 to 60 min after intervention in the EA plus aconitine group (<0.01). Compared with the model group, arrhythmia score was higher in the aconitine group (<0.01). Compared with the aconitine group, arrhythmia score was lower in the EA group and the EA plus aconitine group (<0.01). As compared with the control group, the expression of SERCA2a protein in the left ventricular cardiomyocytes was decreased (<0.01), while the expression of PLB protein was increased in the model group (<0.01). Compared with the model group, the expression of SERCA2a protein was increased in both the EA group and the EA plus aconitine group (<0.05, <0.01), and PLB protein expression was decreased in each intervention group respectively (<0.01, <0.05). As compared with the EA group and the aconitine group, the expression of SERCA2a protein was increased and the expression of PLB protein was decreased in the EA plus aconitine group separately (<0.05, <0.01).
The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.
探讨电针通过肌浆网Ca-ATP酶2a（SERCA2a）/受磷蛋白（PLB）参与对乌头碱治疗心力衰竭的协同及减毒作用机制。
将30只SPF级SD大鼠随机分为对照组、模型组、电针组、乌头碱组和电针加乌头碱组，每组6只。通过向右侧股静脉注射高剂量盐酸普萘洛尔溶液建立大鼠急性心力衰竭模型。造模成功的大鼠稳定10分钟后，电针组和电针加乌头碱组于“内关”（PC 6）穴施加电针，采用疏密波，频率2Hz/15Hz，强度3mA，留针30分钟；乌头碱组和电针加乌头碱组大鼠经左侧股静脉注射乌头碱溶液（10μg/kg）。检测左心室收缩压（LVSP）、左心室内压最大上升/下降速率（±dp/dt）等血流动力学指标，观察心律失常类型并进行评分。采用多重荧光Western blot法检测大鼠左心室心肌组织中SERCA2a蛋白和PLB蛋白表达。
与对照组比较，模型组造模后及干预后各时间点LVSP和±dp/dt均降低（<0.01）。与模型组比较，干预后1分钟乌头碱组和电针组±dp/dt升高（<0.01，<0.05），干预后10～60分钟乌头碱组+dp/dt升高，干预后20～60分钟电针组+dp/dt升高（<0.01，<0.05），干预后1分钟电针组LVSP升高（<0.01），干预后1～60分钟电针加乌头碱组LVSP和±dp/dt均升高（<0.01，<0.05）。与乌头碱组比较，干预后1分钟电针组LVSP和+dp/dt升高（<0.01，<0.05），干预后1分钟电针加乌头碱组LVSP和±dp/dt及干预后20～60分钟+dp/dt均升高（<0.01，<0.05）。与电针组比较，干预后10～60分钟电针加乌头碱组+dp/dt更高（<0.01）。与模型组比较，乌头碱组心律失常评分更高（<0.01）。与乌头碱组比较，电针组和电针加乌头碱组心律失常评分更低（<0.01）。与对照组比较，模型组左心室心肌细胞SERCA2a蛋白表达降低（<0.01），PLB蛋白表达升高（<0.01）。与模型组比较，电针组和电针加乌头碱组SERCA2a蛋白表达均升高（<0.05，<0.01），各干预组PLB蛋白表达均降低（<0.01，<0.05）。与电针组和乌头碱组比较，电针加乌头碱组SERCA2a蛋白表达升高，PLB蛋白表达降低（<0.05，<0.01）。
电针干预可能通过上调心肌组织中SERCA2a表达、下调PLB表达，实现对乌头碱改善心力衰竭的协同/减毒作用。
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