百会、足三里的长期电针刺激对自发性高血压大鼠血压和心肌肥大的改善作用及其机理
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摘要
目的：高血压引发的心肌肥大和心肌纤维化是高血压病的重要合并症。在控制高血压的同时,减轻心肌肥大和心肌纤维化有重要临床意义。本研究观察长期电针刺激百会、足三里对自发性高血压大鼠(Spontaneously Hypertensive Rat, SHR)血压、心肌肥大和心肌纤维化的抑制作用,探讨其可能的机制。
方法：将6周龄的雄性Wistar大鼠随机分为对照组(Wistar)、非穴位电针刺激组(Wistar-NAP)、百会+足三里电针刺激组(Wistar-AP),将6周龄的雄性SHR大鼠随机分为SHR组(SHR)、非穴位电针刺激组(SHR-NAP)、百会+足三里电针刺激组(SHR-AP)(每组8只)。百会+足三里电针刺激组,于入组后周一、三、五上午9-11点之间,用0.35×20mm毫针,在百会穴向背部方向以30°角斜刺入1cm,在右下肢外侧足三里穴,直刺入0.5cm。非穴位电针刺激组,在大鼠尾部距离根部1cm和2cm处,用0.35×20mm毫针,向尾根部方面15。角刺入0.5cm。用韩氏电针仪HANS-202A,1mA,2Hz,持续电刺激20min。对照组只捆绑不针刺和电刺激。于入组后,第一次电针刺激前、电针刺激开始后的第2周、第4周、第6周、第8周周末上午9-11点,用尾套法测量血压。在8周周末,用超声心动仪检测大鼠心室厚度和功能,测心重体重比。取外周血,用ELISA法检测血浆中血管紧张素II (Angiotensin Ⅱ, AngⅡ)、内皮素-1(endothelin-1,ET-1)和一氧化氮(nitric oxide, NO)的含量。取心脏和主动脉升支,观察形态学变化,用免疫组化和Western blotting方法,观察和分析大鼠心肌组织和主动脉升支中血管紧张素1受体(angiotensin Ⅱ type1receptor, AT1R)、内皮素A受体(endothelin-1type A receptor, ETAR)、内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)和诱导型一氧化氮合酶(induced nitric oxide synthase, iNOS)的蛋白表达。
结果：长期电针刺激百会、足三里显著地抑制了SHR大鼠平均动脉压的升高、主动脉壁的增厚、心室厚度的增加,心脏功能的降低,心重体重比的增加；显著地抑制了SHR大鼠血浆中AngⅡ、ET-1的升高和NO含量的降低；显著地抑制了心肌与主动脉中AT1R、 ETAR及iNOS的蛋白表达的升高,增加了eNOS的蛋白表达。
结论：长期电针刺激百会、足三里可抑制SHR大鼠血压的升高,减轻心肌肥大和主动脉壁的肥厚,该作用与其抑制外周血AngⅡ、ET-1的生高,NO的降低,抑制心肌组织和主动脉AT1R、ETAR、iNOS蛋白的表达,促进eNOS的蛋白表达相关。
The purpose of this study is to investigate the inhibitory effects of long term electroacupuncture stimulation at BaiHui (DU20) and ZuSanLi (ST36) on blood pressure, myocardial hypertrophy and myocardial fibrosis of spontaneous hypertension rat (SHR) and underlying mechanisms.6-weeks-old SHR or Wistar male rats were randomly divided into6groups, the control group (SHR/Wistar), the non-acupoint electroacupuncture stimulation group (SHR-NAP/Wistar-NAP) and the electroacupuncture stimulation at DU20and ST36group (SHR-AP/Wistar-AP), with24rats in each group. For SHR-AP/Wistar-AP group and SHR-NAP/Wistar-NAP group, the points locating is according to the Chinese Rat Acupoint Positioning Standard. For the control groups, the rats only were binding up without acupuncture and electrical stimulation. Blood pressure was determined before and at2,4,6, and8weeks after electroacupuncture treatment by the tail-cuff method. At the end of8th weekend, the ventricular thickness and heart function of the rat were detected utilizing echocardiography. The content of angiotensin Ⅱ (Ang Ⅱ), endothelin-1(ET-1) and nitric oxide (NO) in the plasma were determined using enzyme-linked immunosorbent assay. Histological studies were also performed on the heart and the ascending aorta. The expression of angiotensin Ⅱ type1receptor (AT1R), endothelin-1type A receptor (ETAR), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in rat myocardium and ascending aorta were investigated by the western blotting method. The results demonstrated that mean arterial pressure, aortic wall and ventricular thickness and heart/body weight ratio of SHR were significantly reduced with long term electroacupuncture stimulation at DU20and ST36. The content of Ang Ⅱ, ET-1in SHR plasma decreased while the content of NO increased after electroacupuncture treatment. Long term electroacupuncture significantly inhibited protein expression of AT1R, ETAR and iNOS in rat myocardium and ascending aorta, while enhanced the eNOS expression in SHR. The beneficial effects of long term electroacupuncture stimulation at DU20and ST36on heart function may be related to decrease the content of Ang Ⅱ and ET-1while increase the content of NO in peripheral blood, and inhibit the protein expression of AT1R, ETAR, iNOS in cardiac muscle and aortic wall while enhance the expression of eNOS.
方法：将6周龄的雄性Wistar大鼠随机分为对照组(Wistar)、非穴位电针刺激组(Wistar-NAP)、百会+足三里电针刺激组(Wistar-AP),将6周龄的雄性SHR大鼠随机分为SHR组(SHR)、非穴位电针刺激组(SHR-NAP)、百会+足三里电针刺激组(SHR-AP)(每组8只)。百会+足三里电针刺激组,于入组后周一、三、五上午9-11点之间,用0.35×20mm毫针,在百会穴向背部方向以30°角斜刺入1cm,在右下肢外侧足三里穴,直刺入0.5cm。非穴位电针刺激组,在大鼠尾部距离根部1cm和2cm处,用0.35×20mm毫针,向尾根部方面15。角刺入0.5cm。用韩氏电针仪HANS-202A,1mA,2Hz,持续电刺激20min。对照组只捆绑不针刺和电刺激。于入组后,第一次电针刺激前、电针刺激开始后的第2周、第4周、第6周、第8周周末上午9-11点,用尾套法测量血压。在8周周末,用超声心动仪检测大鼠心室厚度和功能,测心重体重比。取外周血,用ELISA法检测血浆中血管紧张素II (Angiotensin Ⅱ, AngⅡ)、内皮素-1(endothelin-1,ET-1)和一氧化氮(nitric oxide, NO)的含量。取心脏和主动脉升支,观察形态学变化,用免疫组化和Western blotting方法,观察和分析大鼠心肌组织和主动脉升支中血管紧张素1受体(angiotensin Ⅱ type1receptor, AT1R)、内皮素A受体(endothelin-1type A receptor, ETAR)、内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)和诱导型一氧化氮合酶(induced nitric oxide synthase, iNOS)的蛋白表达。
结果：长期电针刺激百会、足三里显著地抑制了SHR大鼠平均动脉压的升高、主动脉壁的增厚、心室厚度的增加,心脏功能的降低,心重体重比的增加；显著地抑制了SHR大鼠血浆中AngⅡ、ET-1的升高和NO含量的降低；显著地抑制了心肌与主动脉中AT1R、 ETAR及iNOS的蛋白表达的升高,增加了eNOS的蛋白表达。
结论：长期电针刺激百会、足三里可抑制SHR大鼠血压的升高,减轻心肌肥大和主动脉壁的肥厚,该作用与其抑制外周血AngⅡ、ET-1的生高,NO的降低,抑制心肌组织和主动脉AT1R、ETAR、iNOS蛋白的表达,促进eNOS的蛋白表达相关。
The purpose of this study is to investigate the inhibitory effects of long term electroacupuncture stimulation at BaiHui (DU20) and ZuSanLi (ST36) on blood pressure, myocardial hypertrophy and myocardial fibrosis of spontaneous hypertension rat (SHR) and underlying mechanisms.6-weeks-old SHR or Wistar male rats were randomly divided into6groups, the control group (SHR/Wistar), the non-acupoint electroacupuncture stimulation group (SHR-NAP/Wistar-NAP) and the electroacupuncture stimulation at DU20and ST36group (SHR-AP/Wistar-AP), with24rats in each group. For SHR-AP/Wistar-AP group and SHR-NAP/Wistar-NAP group, the points locating is according to the Chinese Rat Acupoint Positioning Standard. For the control groups, the rats only were binding up without acupuncture and electrical stimulation. Blood pressure was determined before and at2,4,6, and8weeks after electroacupuncture treatment by the tail-cuff method. At the end of8th weekend, the ventricular thickness and heart function of the rat were detected utilizing echocardiography. The content of angiotensin Ⅱ (Ang Ⅱ), endothelin-1(ET-1) and nitric oxide (NO) in the plasma were determined using enzyme-linked immunosorbent assay. Histological studies were also performed on the heart and the ascending aorta. The expression of angiotensin Ⅱ type1receptor (AT1R), endothelin-1type A receptor (ETAR), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in rat myocardium and ascending aorta were investigated by the western blotting method. The results demonstrated that mean arterial pressure, aortic wall and ventricular thickness and heart/body weight ratio of SHR were significantly reduced with long term electroacupuncture stimulation at DU20and ST36. The content of Ang Ⅱ, ET-1in SHR plasma decreased while the content of NO increased after electroacupuncture treatment. Long term electroacupuncture significantly inhibited protein expression of AT1R, ETAR and iNOS in rat myocardium and ascending aorta, while enhanced the eNOS expression in SHR. The beneficial effects of long term electroacupuncture stimulation at DU20and ST36on heart function may be related to decrease the content of Ang Ⅱ and ET-1while increase the content of NO in peripheral blood, and inhibit the protein expression of AT1R, ETAR, iNOS in cardiac muscle and aortic wall while enhance the expression of eNOS.
引文
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