电针内关、神门、合谷对心肌肥厚模型大鼠ERK通路影响的比较研究
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摘要
目前,临床研究证实针灸能有效改善心肌肥厚患者的心功能,实验研究从针刺对缺血心肌功能的调整、心肌细胞结构及血管活性物质的改变、能量代谢障碍的调节、氧自由基生成的减少、抗心肌缺血的中枢神经机制及分子生物学机制等多方面进行了探讨,普遍认为针刺能够积极有效保护心肌细胞。但未见从细胞外信号调节激酶ERK研究电针不同经脉(穴)治疗心肌肥厚的相关报道。本实验试图从与心相关的内关穴及与心无直接联系但处于同一解剖水平段的神门、合谷穴对心肌肥大损伤调整作用予以对比研究。
目的：
本课题拟在中医针灸“胸胁内关谋”临床经验的指导下,借鉴针灸治未病的学术特点,从细胞、分子水平研究针刺对心肌肥厚模型大鼠心肌组织病理形态结构、心电活动、神经内分泌系统CA类神经递质以及AngⅡ和ET、ERK信号通路的调节机制,并比较心经、心包经、大肠经上处于同一解剖水平段的神门、内关、合谷三组穴位间的疗效,为经脉(穴)-脏腑相关提供实验依据。
方法：
采用三月龄清洁级雌性SD大鼠105只,体重171±4.2g,随机数字表法分为7组：正常组,模型组,神门组,内关组,合谷组,抑制剂组,内关+抑制剂组,每组15只。采用经典的皮下注射盐酸异丙肾上腺素制备大鼠左心室心肌肥厚模型,电针内关、神门、合谷穴进行比较。针刺操作方法：造模同时分别针刺大鼠双侧上述3穴,大鼠穿自制鼠衣,用Φ0.30mm×15mm毫针直刺穿皮达筋间,捻转1min后,接HANS-200型电针治疗仪,左右各接一电极,连续波,频率2Hz,强度1mA,通电治疗20min,14d。抑制剂PD98059以0.3mg/kg/d的剂量腹腔注射进行干预。所有大鼠实验结束后称取体重,待心电图观察结束后取材：心内采血取血浆,然后摘取心脏分离左心室称重,计算心肌肥厚指数。取左心室游离壁中部心室肌,显微镜下观察心肌细胞病理结构；HPLC检测血浆中儿茶酚胺类递质及代谢产物含量；放射免疫法检测心肌组织Ang Ⅱ、ET含量；免疫印迹法检测左心室ERK1/2、p-ERK蛋白的表达,并对数据进行统计分析。
结果：
1.针刺对大鼠心肌组织病理结构的影响：正常大鼠心肌纤维排列整齐,毛细血管丰富,内皮细胞未见水肿；心肌细胞形态完整,细胞核电子密度均匀,核仁完整,细胞凋亡较少见；肌丝及肌小节结构清晰可见,线粒体丰富,结构完好,胞质内细胞器结构清晰可见,未见水肿及空泡变。造模后,大鼠心肌细胞光学显微镜下主要表现为以下三个方面：心肌纤维排列紊乱,心肌间质增生,心肌间质纤维化；透射电镜下主要表现为以下六个方面：线粒体肿胀、细胞凋亡增多、内皮细胞间质增生、肌浆网扩张、收缩带收缩不同步、闰盘变形。其余5组大鼠在上述六方面均有不同程度的改善；
2.针刺对大鼠心电图的影响：实验观察到,大鼠造模后心电图ST段,R-R间期于造模14d后明显升高,而心率明显降低,与正常组比较,有极显著性差异(ST段,R-R间期,P<0.05；心率,P<0.01)；抑制剂干预及电针治疗后,大鼠心率、心电图ST段及R-R间期趋于正常,与模型组比较,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
3.针刺对大鼠心肌肥厚指数的影响：大鼠造模后心脏质量明显增加,与正常组相比,有极显著性差异(P<0.01),其余各组间比较无显著性差异(P>0.05)；大鼠全心质量指数和左心室质量指数于造模14d后明显升高,与正常组比较,有极显著性差异(P<0.01)；抑制剂干预及电针治疗后,大鼠全心质量指数和左心室质量指数明显降低,与模型组比较,有显著性差异(P<0.05),三组穴位相比尤以合谷显著(P<0.05),其余各组间比较无显著性差异(P>0.05)；
4.针刺对大鼠血浆中儿茶酚胺类神经递质的影响：大鼠血浆中儿茶酚胺类神经递质(NE.E.DA;肾上腺素、去甲肾上腺素、多巴胺)及代谢产物(NHPG、HVA、DOPAC；3-甲氧基-4-羟基苯乙二醇、高香草酸、3,4-二羟基苯乙酸)含量于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠儿茶酚胺类神经递质及其代谢产物含量减少,与模型组比较,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
5.针刺对大鼠心肌组织中Ang Ⅱ和ET的影响：大鼠心肌组织中AngⅡ和ET含量于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠心肌组织AngⅡ和ET含量减少,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
6.针刺对大鼠左心室心肌组织中ERK1/2、p-ERK的影响：大鼠左心室心肌组织ERK1/2、p-ERK蛋白的表达高于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠左心室心肌组织ERK1/2、p-ERK表达降低,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)
结论：
1.对比心肌肥厚指数发现,内关、神门与合谷三组穴位对心肌保护作用有差异,合谷穴作用明显,在其余指标中有优于内关和神门的趋势,说明合谷在心肌肥厚中发挥了对心脏较好的保护作用,有待进一步探讨。
2.针刺对心肌细胞有明显的保护作用,为经脉(穴)-脏腑相关提供了实验依据,同时发现合谷也有较好的疗效,为临床选穴提供了实验依据。
3.电针通过神经内分泌因子调节ERK信号通路,实现对心肌细胞的保护作用,促进心肌组织形态和超微结构的恢复、改善心电活动。
In recent years, plenty of clinical research verified that acupuncture could improve cardiac function of patients with myocardial hypertrophy. Experimental studies on electroacupuncture (EA) were discussed from the regulation of ischemic myocardial function, change of myocardial cell structure and vasoactive substances, regulation of energy metabolism, reduction of oxygen free radicals, central nervous mechanisms and molecular biological mechanisms of anti-ischemic and many other aspects, EA was generally considered positive and effective to protect myocardial cells. However, the comparative study of EA effects has not been reported from the perspective of extracellular signal regulated kinase (ERK). This experiment tries to give a contrast research that Neiguan acupoint and Shenmen, Hegu at the same anatomical level adjust to myocardial hypertrophy injure.
Objective:
This subject is intended under the guidance of Chinese acupuncture theory "for heart and chest, it is point Neiguan", draw on the academic characteristic of acupuncture on prevention of disease, in order to study the pathology morphological structure of myocardial tissue, regulatory mechanisms of cardiac electrophysiology, catecholamine neurotransmitter, angiotensin II and endothelin in neuroendocrine system and ERK signaling pathway in cardiac hypertrophic model rats from the cellular and molecular levels; Try to have a comparative study between H7, PC6 and LI4at the same anatomical level on heart meridian, pericardium meridian and large intestine meridian; To explore specificity of the correlation between meridians (acupoint) and viscera, and provide the experimental basis.
Methods:
One hundred and five clean three-month-old female SD rats, weigh about171±4.2g, were randomly divided into seven groups by random number table method:normal group, model group, H7group, PC6group, LI4group, inhibitor group and PC6added inhibitor group, with fifteen rats in each group respectively. Rats were treated in a classic method with injection of isoprenaline hydrochlorid in the back skin to prepare left ventricular hypertrophy model, three sets of acupuncture effect (PC6, H7and LI4) were compared. Acupuncture operating method:the acupuncture needle,15mm long and0.3mm in diameter, was penetrated into the subcutis and rotated for1minute. The bilateral acupoints were interconnected with a Hans acupoint nerve stimulator (HANS) EA apparatus, and the following stimulus parameters were selected: continuous-wave at2Hz and1mA,20minutes a day for14days, and inhibitor intervention was used in the experiment with a calculate of3mg/kg/d through intraperitoneal injection. All rats were weighed the body weight after the end of the experiment, and then were taken tissue biopsy after electrocardiogram (ECG). After obtained blood plasma by heart picks, cardiac were gathered and weighted, myocardial hypertrophy indexes were calculated, and then the central ventricle muscle of LVFW (left ventricle free wall) was separated from the cardiac. The muscle was inspected the myocardial cell pathological structure under microscope; Content of plasma catecholamine neurotransmitters and metabolin were detected through HPLC (High Performance Liquid Chromatography); The cardiac tissue Ang Ⅱ (Angiotensin Ⅱ) and ET (Endothelin) was analyzed by radioimmunoassay; Protein expression of left ventricular ERK1/2and p-ERK was detected by western blot, and the data were analyzed through a statistical analysis system at last.
Results:
1. Effect of acupuncture on the pathological structure of myocardial tissue: normal rats'cardiac muscle fibers arranged in neat rows, with abundant capillaries, without edema in endothelial cells; Myocardial cells appeared morphological integrity, the nucleus electronic density distribute homogeneous, with complete nucleoli and rare apoptosis; Myofilament and sarcomere structure was clearly visible, with abundant and intact mitochondria, and cytoplasmic organelle structure is clearly visible without edema and vacuolization. After modeling, rats'myocardial cells under an optical microscope appeared mainly for the following three aspects:including disorganized cardiac muscle fibres, proliferating myocardial interstitium, and fiberized myocardial interstitium. For the following six areas under transmission electron microscopy:including mitochondria swelling, increasing cell apoptosis, endothelial cell interstitial hyperplasia, muscle plasma nets expansion, out-sync contraction of contraction band, and intercalated disc deformation. Rats in the other five groups were improved to some degree in the above six aspects;
2. Effect of acupuncture on myocardial hypertrophy index in rats: abtained from the experiment, the rats'heart weight in model group were increased significantly while compared with normal group (P<0.01), but no significant differences were found in other groups (P>0.05); Compared with the normal group, HWIs and LVWIs in the model group were significantly higher after modeling for14days (P<0.01); After the inhibitor intervention and electro-acupuncture treatment, the HWIs and LVWIs were significantly lower than modle group (P<0.05), especially LI4group was significantly changed while compared between three EA groups (P<0.05), but no significant differences were found in other groups (P>0.05);
3. Effect of acupuncture on ECG in rats:abtained from the experiment, compared with those in the normal group, ST segment and R-R interval were significantly higher, and the heart rate was lower in the model group after modeling for14days (P<0.05; P<0.01); After the inhibitor intervention and electro-acupuncture treatment, the heart rate, ST segment and R-R interval significantly tended to be normal while compared with modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
4. Effect of acupuncture on plasma catecholamine neurotransmitter in rats: compared with those in the normal group, content of plasma catecholamine neurotransmitters (NE, E and DA) and metabolin (MHPG, HVA and DOPAC) was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, content of plasma catecholamine neurotransmitters and metabolin was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
5. Effect of acupuncture on the cardiac tissue AngⅡand ET in rats: compared with those in the normal group, content of the cardiac tissue Ang Ⅱ and ET was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, content of the cardiac tissue Ang Ⅱ and ET was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
6. Effect of acupuncture on the left ventricular myocardial tissue ERK1/2and p-ERK in rats:compared with those in the normal group, protein expression of the left ventricular myocardial tissue ERK1/2and p-ERK was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, ERK1/2and p-ERK expression was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05).
Conclusion
1. Contrast myocardial hypertrophy index, there's a difference between PC6, H7and LI4on the protective effect on myocardium, LI4group was significant, and was superior in other targets while compared with PC6and H7groups. Possibly LI4analgesic effect played a protective effect in myocardial hypertrophy.
2. Acupuncture had a significant protective effect on myocardial cells, which provided experimental evidence on the relation between meridians (acupoints) and viscera; Meanwhile LI4was found effective on MH, which also provided an experimental basis for clinical selection of acupoints.
3. We were able to verify that acupuncture indeed improve cardiac function in MH, and this effect had a close relation with ERK signaling pathways through regulating the role of neuroendocrine-cytokines to promote the organization forms and myocardial ultrastructure of rehabilitation, improve ECG activities.
目的：
本课题拟在中医针灸“胸胁内关谋”临床经验的指导下,借鉴针灸治未病的学术特点,从细胞、分子水平研究针刺对心肌肥厚模型大鼠心肌组织病理形态结构、心电活动、神经内分泌系统CA类神经递质以及AngⅡ和ET、ERK信号通路的调节机制,并比较心经、心包经、大肠经上处于同一解剖水平段的神门、内关、合谷三组穴位间的疗效,为经脉(穴)-脏腑相关提供实验依据。
方法：
采用三月龄清洁级雌性SD大鼠105只,体重171±4.2g,随机数字表法分为7组：正常组,模型组,神门组,内关组,合谷组,抑制剂组,内关+抑制剂组,每组15只。采用经典的皮下注射盐酸异丙肾上腺素制备大鼠左心室心肌肥厚模型,电针内关、神门、合谷穴进行比较。针刺操作方法：造模同时分别针刺大鼠双侧上述3穴,大鼠穿自制鼠衣,用Φ0.30mm×15mm毫针直刺穿皮达筋间,捻转1min后,接HANS-200型电针治疗仪,左右各接一电极,连续波,频率2Hz,强度1mA,通电治疗20min,14d。抑制剂PD98059以0.3mg/kg/d的剂量腹腔注射进行干预。所有大鼠实验结束后称取体重,待心电图观察结束后取材：心内采血取血浆,然后摘取心脏分离左心室称重,计算心肌肥厚指数。取左心室游离壁中部心室肌,显微镜下观察心肌细胞病理结构；HPLC检测血浆中儿茶酚胺类递质及代谢产物含量；放射免疫法检测心肌组织Ang Ⅱ、ET含量；免疫印迹法检测左心室ERK1/2、p-ERK蛋白的表达,并对数据进行统计分析。
结果：
1.针刺对大鼠心肌组织病理结构的影响：正常大鼠心肌纤维排列整齐,毛细血管丰富,内皮细胞未见水肿；心肌细胞形态完整,细胞核电子密度均匀,核仁完整,细胞凋亡较少见；肌丝及肌小节结构清晰可见,线粒体丰富,结构完好,胞质内细胞器结构清晰可见,未见水肿及空泡变。造模后,大鼠心肌细胞光学显微镜下主要表现为以下三个方面：心肌纤维排列紊乱,心肌间质增生,心肌间质纤维化；透射电镜下主要表现为以下六个方面：线粒体肿胀、细胞凋亡增多、内皮细胞间质增生、肌浆网扩张、收缩带收缩不同步、闰盘变形。其余5组大鼠在上述六方面均有不同程度的改善；
2.针刺对大鼠心电图的影响：实验观察到,大鼠造模后心电图ST段,R-R间期于造模14d后明显升高,而心率明显降低,与正常组比较,有极显著性差异(ST段,R-R间期,P<0.05；心率,P<0.01)；抑制剂干预及电针治疗后,大鼠心率、心电图ST段及R-R间期趋于正常,与模型组比较,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
3.针刺对大鼠心肌肥厚指数的影响：大鼠造模后心脏质量明显增加,与正常组相比,有极显著性差异(P<0.01),其余各组间比较无显著性差异(P>0.05)；大鼠全心质量指数和左心室质量指数于造模14d后明显升高,与正常组比较,有极显著性差异(P<0.01)；抑制剂干预及电针治疗后,大鼠全心质量指数和左心室质量指数明显降低,与模型组比较,有显著性差异(P<0.05),三组穴位相比尤以合谷显著(P<0.05),其余各组间比较无显著性差异(P>0.05)；
4.针刺对大鼠血浆中儿茶酚胺类神经递质的影响：大鼠血浆中儿茶酚胺类神经递质(NE.E.DA;肾上腺素、去甲肾上腺素、多巴胺)及代谢产物(NHPG、HVA、DOPAC；3-甲氧基-4-羟基苯乙二醇、高香草酸、3,4-二羟基苯乙酸)含量于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠儿茶酚胺类神经递质及其代谢产物含量减少,与模型组比较,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
5.针刺对大鼠心肌组织中Ang Ⅱ和ET的影响：大鼠心肌组织中AngⅡ和ET含量于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠心肌组织AngⅡ和ET含量减少,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)；
6.针刺对大鼠左心室心肌组织中ERK1/2、p-ERK的影响：大鼠左心室心肌组织ERK1/2、p-ERK蛋白的表达高于造模14d后明显升高,与正常组比较,有显著性差异(P<0.05)；抑制剂干预及电针治疗后,大鼠左心室心肌组织ERK1/2、p-ERK表达降低,有显著性差异(P<0.05),其余各组间比较无显著性差异(P>0.05)
结论：
1.对比心肌肥厚指数发现,内关、神门与合谷三组穴位对心肌保护作用有差异,合谷穴作用明显,在其余指标中有优于内关和神门的趋势,说明合谷在心肌肥厚中发挥了对心脏较好的保护作用,有待进一步探讨。
2.针刺对心肌细胞有明显的保护作用,为经脉(穴)-脏腑相关提供了实验依据,同时发现合谷也有较好的疗效,为临床选穴提供了实验依据。
3.电针通过神经内分泌因子调节ERK信号通路,实现对心肌细胞的保护作用,促进心肌组织形态和超微结构的恢复、改善心电活动。
In recent years, plenty of clinical research verified that acupuncture could improve cardiac function of patients with myocardial hypertrophy. Experimental studies on electroacupuncture (EA) were discussed from the regulation of ischemic myocardial function, change of myocardial cell structure and vasoactive substances, regulation of energy metabolism, reduction of oxygen free radicals, central nervous mechanisms and molecular biological mechanisms of anti-ischemic and many other aspects, EA was generally considered positive and effective to protect myocardial cells. However, the comparative study of EA effects has not been reported from the perspective of extracellular signal regulated kinase (ERK). This experiment tries to give a contrast research that Neiguan acupoint and Shenmen, Hegu at the same anatomical level adjust to myocardial hypertrophy injure.
Objective:
This subject is intended under the guidance of Chinese acupuncture theory "for heart and chest, it is point Neiguan", draw on the academic characteristic of acupuncture on prevention of disease, in order to study the pathology morphological structure of myocardial tissue, regulatory mechanisms of cardiac electrophysiology, catecholamine neurotransmitter, angiotensin II and endothelin in neuroendocrine system and ERK signaling pathway in cardiac hypertrophic model rats from the cellular and molecular levels; Try to have a comparative study between H7, PC6 and LI4at the same anatomical level on heart meridian, pericardium meridian and large intestine meridian; To explore specificity of the correlation between meridians (acupoint) and viscera, and provide the experimental basis.
Methods:
One hundred and five clean three-month-old female SD rats, weigh about171±4.2g, were randomly divided into seven groups by random number table method:normal group, model group, H7group, PC6group, LI4group, inhibitor group and PC6added inhibitor group, with fifteen rats in each group respectively. Rats were treated in a classic method with injection of isoprenaline hydrochlorid in the back skin to prepare left ventricular hypertrophy model, three sets of acupuncture effect (PC6, H7and LI4) were compared. Acupuncture operating method:the acupuncture needle,15mm long and0.3mm in diameter, was penetrated into the subcutis and rotated for1minute. The bilateral acupoints were interconnected with a Hans acupoint nerve stimulator (HANS) EA apparatus, and the following stimulus parameters were selected: continuous-wave at2Hz and1mA,20minutes a day for14days, and inhibitor intervention was used in the experiment with a calculate of3mg/kg/d through intraperitoneal injection. All rats were weighed the body weight after the end of the experiment, and then were taken tissue biopsy after electrocardiogram (ECG). After obtained blood plasma by heart picks, cardiac were gathered and weighted, myocardial hypertrophy indexes were calculated, and then the central ventricle muscle of LVFW (left ventricle free wall) was separated from the cardiac. The muscle was inspected the myocardial cell pathological structure under microscope; Content of plasma catecholamine neurotransmitters and metabolin were detected through HPLC (High Performance Liquid Chromatography); The cardiac tissue Ang Ⅱ (Angiotensin Ⅱ) and ET (Endothelin) was analyzed by radioimmunoassay; Protein expression of left ventricular ERK1/2and p-ERK was detected by western blot, and the data were analyzed through a statistical analysis system at last.
Results:
1. Effect of acupuncture on the pathological structure of myocardial tissue: normal rats'cardiac muscle fibers arranged in neat rows, with abundant capillaries, without edema in endothelial cells; Myocardial cells appeared morphological integrity, the nucleus electronic density distribute homogeneous, with complete nucleoli and rare apoptosis; Myofilament and sarcomere structure was clearly visible, with abundant and intact mitochondria, and cytoplasmic organelle structure is clearly visible without edema and vacuolization. After modeling, rats'myocardial cells under an optical microscope appeared mainly for the following three aspects:including disorganized cardiac muscle fibres, proliferating myocardial interstitium, and fiberized myocardial interstitium. For the following six areas under transmission electron microscopy:including mitochondria swelling, increasing cell apoptosis, endothelial cell interstitial hyperplasia, muscle plasma nets expansion, out-sync contraction of contraction band, and intercalated disc deformation. Rats in the other five groups were improved to some degree in the above six aspects;
2. Effect of acupuncture on myocardial hypertrophy index in rats: abtained from the experiment, the rats'heart weight in model group were increased significantly while compared with normal group (P<0.01), but no significant differences were found in other groups (P>0.05); Compared with the normal group, HWIs and LVWIs in the model group were significantly higher after modeling for14days (P<0.01); After the inhibitor intervention and electro-acupuncture treatment, the HWIs and LVWIs were significantly lower than modle group (P<0.05), especially LI4group was significantly changed while compared between three EA groups (P<0.05), but no significant differences were found in other groups (P>0.05);
3. Effect of acupuncture on ECG in rats:abtained from the experiment, compared with those in the normal group, ST segment and R-R interval were significantly higher, and the heart rate was lower in the model group after modeling for14days (P<0.05; P<0.01); After the inhibitor intervention and electro-acupuncture treatment, the heart rate, ST segment and R-R interval significantly tended to be normal while compared with modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
4. Effect of acupuncture on plasma catecholamine neurotransmitter in rats: compared with those in the normal group, content of plasma catecholamine neurotransmitters (NE, E and DA) and metabolin (MHPG, HVA and DOPAC) was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, content of plasma catecholamine neurotransmitters and metabolin was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
5. Effect of acupuncture on the cardiac tissue AngⅡand ET in rats: compared with those in the normal group, content of the cardiac tissue Ang Ⅱ and ET was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, content of the cardiac tissue Ang Ⅱ and ET was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05);
6. Effect of acupuncture on the left ventricular myocardial tissue ERK1/2and p-ERK in rats:compared with those in the normal group, protein expression of the left ventricular myocardial tissue ERK1/2and p-ERK was significantly higher in the model group after modeling for14days (P<0.05); After the inhibitor intervention and electro-acupuncture treatment, ERK1/2and p-ERK expression was significantly lower than modle group (P<0.05), but no significant differences were found in other groups (P>0.05).
Conclusion
1. Contrast myocardial hypertrophy index, there's a difference between PC6, H7and LI4on the protective effect on myocardium, LI4group was significant, and was superior in other targets while compared with PC6and H7groups. Possibly LI4analgesic effect played a protective effect in myocardial hypertrophy.
2. Acupuncture had a significant protective effect on myocardial cells, which provided experimental evidence on the relation between meridians (acupoints) and viscera; Meanwhile LI4was found effective on MH, which also provided an experimental basis for clinical selection of acupoints.
3. We were able to verify that acupuncture indeed improve cardiac function in MH, and this effect had a close relation with ERK signaling pathways through regulating the role of neuroendocrine-cytokines to promote the organization forms and myocardial ultrastructure of rehabilitation, improve ECG activities.
引文
[1]刘俊岭,陈振荣.“九五”国家攀登计划预选项目“经络的研究”进展.针刺研究.2002；27(3)：230-237.
[2]周凤梧,张奇文,丛林.名老中医之路[M].济南：山东科学技术出版社,2005：181.
[3]Kuusisto J, Karja V, Sipola P, et al. Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy [J]. Heart.2012 Mar 24. [Epub ahead of print]
[4]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[5]Izzo JL Jr, Gradman AH. Machanisms and management of hypertensive heart disease:from left ventrie hypertrophy to heart failure [J]. Med Clin North Am, 2004; 88 (5):1257-1271.
[6]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-repeffusion injury by inhibiting events in the early minutes of reperfusian [J]. Cardiovasc Res.2004; 62(1):74-85.
[7]Sun HY, Wang NP, Kerendi F, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+overload [J]. Am J Physiol Heart Circ Physiol,2005; 288(4):H1900-1908.
[8]吴刚,杨蕾,刘永锋,等.缺血预处理对大鼠肝脏缺血再灌注损伤保护作用机制的研究[J].中华肝胆外科杂志,2003；9(4)：221-224.
[9]Alvarez-Jaimes L, Feliciano-Rivera M, Centeno-Gonzalez M, et al. Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens [J]. J Pharmacol Exp Ther 2005; 314(3):1144-1157.
[10]Bonni A, Brunet A,West A E, et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms [J]. Science,1999; 286(5443):1358-1362.
[11]Haq S, Choukroun G, Lim H, et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure [J]. Circulation,2001; 103(5):670-677.
[12]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[13]Wang L, Proud CG. Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes [J]. Circ. Res,2002; 91(9):821-829.
[14]王祥,戴友平,杨杪,等.心房颤动心房组织内细胞外信号调节激酶和血管紧张素转化酶表达的研究[J].中华心血管病杂志,2004；32(3)：207-210.
[15]王春雷,王升旭,龚伟.佐剂关节炎大鼠脊髓背角内磷酸化ERK在电针夹脊穴镇痛中的变化[J].上海针灸杂志,2005；24(12)：33-35.
[16]姜雪梅,原林,张学全,等.针刺对大鼠局部筋膜和脊髓细胞外信号调节激酶1/2和P38丝裂酶原活化蛋白激酶信号通路的影响[J].中国康复医学杂志,2009；24(11)：973-976.
[17]Guan X, Wu HG, Ma XP, et al. Experimental Research of Electroacupuncture on ERK Phosphorylation in Rats of Hepatofibrosis [J]. J Acupunct. Tuina. Sci,2009; 5(7):270-273.
[18]张威,马贤德,王健.眼针对脑缺血再灌注模型大鼠ERK1/2信号转导通路影响的实验研究[J].中国医科大学学报,2012；41(1)：42-44.
[19]尤行宏,陈泽斌,王华,等.内阿片肽在“双固一通”针法保护缺血心肌中的作用[J].中国老年学杂志,2010；12(30)：3686-3688.
[20]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠肥厚心肌病理组织学影响的研究[J].世界中西医结合杂志,2008；3(6)：319-321.
[21]王华,喻建兵,吴绪平,等.电针郄门穴对室性心动过速模型大鼠心率及血浆一氧化氮含量的影响[J].2010；51(9)：814-816.
[22]吴松,唐宏图,陈泽斌,等.“双固一通”针法对急性心肌缺血模型大鼠心肌组织过氧化物酶活性的影响[J].湖北中医杂志,2006；28(10)：3-5.
[23]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠心肌SOD、GSH-PX活性和MDA含量的影响[J].湖北中医学院学报,2006；8(2)：15-16.
[24]尤行宏,王华,陈泽斌,等.延髓内阿片肽对电针抗心肌缺血效应的影响,现代中西医结合杂志[J].2009；18(29)：3541-3544.
[25]李明磊,王华,陈泽斌.电针内关穴对AMI大鼠自主神经与中枢P物质、一氧化氮合酶的影响[J].中华中医药杂志,2007；22(8)：543-546.
[26]王华,邓丽霞,吴绪平,等.电针“内关”对室性心动过速大鼠心率及血浆儿茶酚胺含量的影响[J].针刺研究,2009；34(3)：180-182.
[27]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠Ang Ⅱ、ET及CGRP的影响[J].中国康复,2008；23(3)：150-151.
[28]Radzievsky SA, Lebedeva OD, Fisenko LA, et al. Function of myocardial contraction and relaxation in essential hypertension in dynamics of acupuncture therapy [J]. Am J Chin Med,1989; 17(3-4):111-117.
[1]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocyte hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[2]Yin W, Zhang P, Huang JH, et al. Stimulation of kappa-opioid receptor reduces isoprenaline-induced cardiac hypertrophy and fibrosis [J]. Eur J Pharmacol,2009; 607(1-3):135-142.
[3]Kitagawa Y, Yamashita D, Ito H, et al. Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts [J]. Am J Physiol Heart Circ Physiol,2004; 287(1):H277-H285.
[4]Bos R, Mougenot N, Findj i L, et al. Inhibition of catecholamine-induced cardiac fibrosis by an aldosterone antagonist [J]. Cardiovasc Pharmacol,2005; 45(1): 8-13.
[5]Li L, Zhang LK, Pang YZ, et al. Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury 38induced by isoproterenol in rats [J]. Acta Pharmacol Sin,2006; 27(5):527-535.
[6]沈楠,王艳春,范红艳,等.异丙肾上腺素致大鼠心肌肥厚及对相关因子的影响[J].吉林医药学院学报,2007；28(3)：141-143.
[7]Tang XD, Zhou X, Zhou KY. Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor lalpha protein accumulation and vascular endothelial growth factor expression in human breast cancer cells [J]. Acta Pharmacol Sin,2009; 30(5):605-616.
[8]Kui L, Weiwei Z, Ling L, et al. Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway [J]. Regul Pept,2009; 155(1-3):62-69.
[9]Alessi DR, Cuenda A, Cohen P, et al. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo [J]. J Biol Chem,1995; 270(46):27489-27494.
[10]Zheng JJ, Chen C, Wang G, et al. Effect of MEK1 inhibitor PD98059 on the signal transduction of Tec in HepG2 hepatoma cells [J]. Chinese-German Journal of Clinical Oncology,2007; 6(6):542-545.
[11]吴珍,李胜保,童强.PD98059对食管癌细胞放射敏感性影响的研究[J].临床消化病杂志,2009；21(4)：198-200.
[12]Hsu CC, Weng CS, Liu TS, et al. Effects of electrical acupuncture on acupoint BL15 evaluated in terms of heart rate variability, pulse rate variability and skin conductance response [J]. Am J Chin Med,2006; 34(1):23-36.
[13]Zhou W, Fu LW, Tjen-A-Looi SC, et al. Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses [J]. J Appl Physiol,2005; 98(3):872-880.
[14]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[15]昊钟琪,赵祥文.现代诊疗新技术,长沙：湖南科学技术出版社[M].1987：249-252.
[16]Boluyt M O, Long X, Eschenhagen T, et al. Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart [J]. Am J Physiol Heart Circ Physiol,1995; 269(2 Pt 2):H638-H647.
[17]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocite hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[18]Ivens E. Hypertrophic cardiomyopathy. Heart Lung Circ,2004; 13 Suppl 3: S48-55.
[19]Mann DL. Inflammatory mediators and the failing heart:past, present and the foreseeable future [J]. Circ Res,2002; 91(11):988-998.
[20]Nian M, Lee P, Khaper N, et al. Inflammatory cytokines and postmyocardial infarction remodeling [J]. Circ Res,2004; 94(12):1543-1553.
[21]Aukrust P, Gullestad L, Ueland T, et al. Inflammatory and anti-inflammatory cytokines in chronic heart failure:potential therapeutic implications [J]. Ann Med, 2005; 37(2):74-85.
[22]陈亦人.伤寒论译释[M].上海：上海科学技术出版社,1 992：11-12.
[23]罗明富,王平,刘俊岭,等.电针“内关”穴对家兔急性心肌缺血区肌原纤维、线粒体和血小板的影响[J].针刺研究,2001；26(2)：119-121.
[24]田岳风,严洁,林亚平,等.电针“内关”对心肌缺血再灌注损伤内皮素及超微结构的影响[J].中国针灸,2002；22(8)：547-549.
[1]Shimizu M, Ino H, Yamagychi M, et al. Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin I mutation [J]. Am Heart J,2001; 143(2):289-293.
[2]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[3]黄宛.主编临床心电图学[M]：第5版,北京：人民卫生出版社,2001：23-41.
[4]Kralova E, Mokran T, Murin J, et al. Electrocardiography in two model s of isoproterenol-induced left ventricular remodeling [J]. Physiol Res,2008; (Suppl.2):S83-S89.
[5]Boluyt M O, Long X, Eschenhagen T, et al. Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart [J]. Am J Physiol Heart Circ Physiol,1995; 269(2 Pt 2):H638-H647.
[6]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocyte hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[7]CAM FS, RAY M. Hypertrophic cardiomyopathy:pathological features and molecular pathogenesis [J]. Anadolu Kardiyol Derg,2004; 4(4):327-330.
[8]严洁,刁利红,易受乡,等.电针内关穴对心肌缺血再灌注损伤大鼠心肌能量代谢及组织形态学的影响[J].中国组织工程研究与临床康复,2007；11(47)：9443-9447.
[9]Kim E, Cho JH, Jung WS, et al. Effect of acupuncture on heart rate variability in primary dysmenorrheic women [J]. Am J Chin Med,2011; 39(2):243-249.
[10]Li Z, Wang C, Mak AF, et al. Effects of acupuncture on heart rate variability in normal subjects under fatigue and non-fatigue state [J]. Eur J Appl Physiol,2005; 94(5-6):633-640.
[11]徐俊华,施苗吾,胡丽霞.针刺合谷穴治疗心绞痛初探[J].上海针灸杂志,1993,12(3)：101.
[12]李颖文,刘东生,符文彬.针灸从“四关”穴论治及其临床应用-跟符文彬主任学习心得[A].广东省针灸学会第九次学术交流会论文汇编[C].2004.
[13]林仁勇,吴俊贤,张佩,等.神门穴真、假针刺对心率和心率变异性影响的比较研究[J].时珍国医国药,2012；23(3)：752-754.
[14]林仁勇,陈俊琦,吴秋萍,等.针刺神门穴对心率变异性频域指标影响的研究[J].新中医,2010；42(10)：95-96.
[15]陈俊琦,廖韩波,王娇,等.针刺神门穴与非穴对心率及心率变异性影响的比较研究[J].针刺研究,2011；17(11)：1248-1249.
[16]刘丽芝,陈俊琦,吴秋萍,等.基于心率变异性分析针刺神门穴影响心率的机制[J].针灸临床杂志,2010；26(6)：45-46.
[17]林冬群,林宇,胡佳,等.电针内关、神门穴对冠心病冠脉旁路移植术后心功能的影响[J].现代中西医结合杂志,2009,18(19)：2241-2242.
[18]程斌,谭奇纹.电针对冠心病患者心电图即刻效应的对比观察[J].上海针灸杂志,2008,27(5)：12-14.
[19]周美启,高纺,吴生兵,等.针刺心包经、心经对急性心肌缺血模型大鼠心肌肌钙蛋白T的影响[J].中医药临床杂志,2011；23(11)：951-952.
[20]高纺,吴生兵,曹健,等.针刺心经心包经对急性心肌缺血大鼠心电图J点、T波振幅及心肌梗死面积的影响[J].安徽中医学院学报,2011；30(5)：53-56.
[1]Sunoda M. Role of catecholamine metabolism in blood pressure regulation using chemiluminescence reaction detection [J]. Yakugaku Zasshi,2008; 128(11): 1589-1594.
[2]裴兆辉,朱妙章,裴建明,等.高效液相色谱测定大鼠血浆儿茶酚胺的含量[J].心脏杂志,2003；15(1)：9-11.
[3]Shida M. Role of adrenergic receptor system in canine left ventricular hypertrophy [J]. Kokyu To Junkan,1989; 37(3):321-327.
[4]Cohen J. Role of endocrine factors in the pathogenesis of cardiac hypertrophy [J]. Circ Res,1974; 35(2):supplⅡ:49-57.
[5]Walker DM. Update on epinephrine (adrenaline) for pediatric emergencies [J]. Curr Opin Pediatr,2009; 21(3):313-319.
[6]Prasad AA, Pasterkamp RJ. Axon guidance in the dopamine system [J]. Adv Exp Med Biol,2009; 651:91-100.
[7]Cave JW, Baker H. Dopamine systems in the forebrain [J]. Adv Exp Med Biol, 2009; 651:15-35.
[8]Schindler CW, Karcz-Kubicha M, Thorndike EB, et al. Lack of adenosine Al and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A2A receptor agonist CGS 21680[J]. Eur J Pharmacol,2004; 484(2-3): 269-275.
[9]Hurst RS, Higdon NR, Lawson JA, et al. Dopamine receptor agonists differ in their actions on cardiac ion channels [J]. Eur J Pharmacol,2003; 482 (1-3):31-37.
[10]李佳,刘建民,刘溪泉,等.电针“强壮”穴对亚急性衰老大鼠神经免疫调节的影响[J].中国针灸,2009；29(11)：905-909.
[11]王华,邓丽霞,吴绪平,等.电针“内关”对室性心动过速大鼠心率及血浆儿茶酚胺含量的影响[J].针刺研究,2009；34(3)：180-182.
[12]王祥瑞,王震虹,林函,等.电针刺对缺血再灌注后心肌的保护作用[J].中国药物与临床,2005；5(5)：328-331.
[13]Uchida S, Shimura M, Ohsawa H, Suzuki A. Neural mechanism of bradycardiac responses elicited by acupuncture-like stimulation to a hind limb in anesthetized rats [J]. J Physiol Sci,2007; 57(6):377-382.
[1]Velez Rueda JO, Palomeque J, Mattiazzi A. Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII [J]. J Appl Physiol.2012 Apr 5. PMID:22492934 [Epub ahead of print].
[2]何建桂,黄艺仪,马虹,等.血管紧张素-(1-7)对心肌肥厚的影响及其与细胞外信号调节激酶的关系[J].中国病理生理杂志,2005；21(9)：1713-1716.
[3]姜庆军,徐耕,朱有法.伊贝沙坦和培垛普利对大鼠压力负荷性心肌肥厚的影响[J].中国病理生理杂志,2004；20(5)：827-831.
[4]Dstal D.E, Baker K.M. The cardiac rennin-angiotensin system:conceptual, or a regulator of cardiac function [J]. nCric Res,1999; 85:643-650.
[5]Pelouch V, Kolar F, O stadal B, et al.Regression of chronic hypoxia-induced pulmonary hypertension, pulmonary hypertension, right ventricular hypertrophy, and fibrosis:effect of Enalapriln [J]. Cardiovase Drug Ther,1997; 11(2):177-185.
[6]Golomb E, Abassi Z A, Cude G, et al. Angiotensin 1I maintains, but does not mediate.isoproterenol-induced cardiac hypertrophy in rats [J]. Am J Physiol,1994; 267(4):1496-1506.
[7]秦旭平,龙光,徐立朋,等.氯沙坦和培垛普利逆转高血压大鼠心血管重构 的比较[J].中国药理学通报,2004；20(10)：1107-1111.
[8]Borges JC, Silva JA J r, Gomes MA, et al. Tonin in rat heart with experimental hypertrophy [J]. Am J Physiol Heart Circ Physiol,2003; 284 (6):H2263-2268.
[9]Lorell BH. Role of angiotensin AT1 and AT2 receptors in cardiac hyper trophy and disease [J]. Am J Cardiol,1999; 83(12A):48-52.
[10]Motoaki Sano, Keiichi Fukuda, Toshiniko Sato. ERK and p38MAPK, but not NF-κB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin Ⅱ in cardiac fibroblasts [J]. CircRes,2001; 89(8):661.
[11]Henry E Kim, Seema S Dalal, Erik Young.Disruption of the myocardial extracellular matrix leads to cardiac dysfunction [J]. J Clin Invest,2000; 106(7): 857.
[12]George W Booz, Jonathan N E Day, Kenneth M Baker.I nterplay between the cardiac rennin angiotensin system and JAK-STAT signaling:role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure [J]. J Mol Cell Cardiol,2002; 34(11):1443.
[13]梁敏,林赛娟,梁宁.乌拉地尔对高血压患者血浆4种神经肽含量的影响[J].中华麻醉学杂志,2000；20：24-25.
[14]Mancia GA, White WB. In white coat hypertension innocent or detrimental [J]. Blood Press Monit,1999; 4(5):241-247.
[15]Bass C, Thiene G, Della Barbera M, et al. Endothelin A receptor antagonist administration immediately after experimental myocardial infaretion with reperfusion does not affect scar healing in dogs [J]. Cardiovascnlar research,2002; 55(1):113-121.
[16]Clozel M, Qiu C, Hess P, et al. Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction [J]. J Am Col Cardiol,2002; 239(1):142-147.
[17]Aqnetti G, Bezstarosti k, et al. Proteomic profiling of endothelin-1 stimulated hypertrophic cardiomyoeytes reveals the increase of four different desmin species and alpha-B-crystallin [J].2008; 1784(7-8):1068-107.
[18]Piuhola J, Szokodi I, Kinnunen P, et al. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts [J]. Hypertension,2003; 41(1): 93-99.
[19]You H W, Chen X, You H J, et al. Role of endothelin-1 and its receptors on hypertrophy or proliferation of cultured cardial cells [J]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao,2006; 28(4):520-523.
[20]孔令雷,颜玲娣,宫泽辉.内皮素系统与心肌肥厚[J].中国药理学通报,2008；24(9)：1127-1130.
[21]Choi SR, Jang JS, Lee JH, et al. Role of serum tumor markes in monitoring for recurrence of gastric cancer following radical gastrectomy [J]. Dig Dis Sci,2006; 51(11):2081-2086.
[22]Dohiy, Hahn AW, Boulanger CM, et al. Endothelin stimulated by angiotensin angiotensin contractility of spontaneously hypertensive rat resistance arteries [J]. Hypertension,1992; 19(2):131-137.
[23]DUscio LV, Barton M, Shaw S, et al. Structure and function of small arteries in salt-induced hypertension:effects of chronic endothelin-subtype-A-receptor blockade [J]. Hypertension,1997; 30(4):905-911.
[24]Oriji GK, Keiser HR. Protein Kinase C mediates angiotensin-induced contractions and the release of endothelin and prostacyclin in rat aortic rings. Prostag landins leukotrienes [J]. Essential Fatty Acids,1997; 57(2):135-141.
[25]Luscher TF. Endothelial dysfunction:the role and impact of the rennin angiotensin system [J]. Heart,2000; 84(1):i20-22.
[26]Ruiz-Opazo N, Hirayama K, et al. Molcecular characterization of a dual endothelin-1/Angiotensin Ⅱ receptor. Mol Med,1998; 4(2):96-108.
[1]Ritchie RH, Irvine JC, Rosenkranz AC, et al. Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy:NON and beyond [J]. Pharmacol Ther,2009; 124(3):279-300.
[2]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[3]Ritchie RH, Rosenkranz AC, Huynh LP, et al. Activation of IP prostanoid receptors prevents cardiomyocyte hypertrophy via cAMP-dependent signaling [J]. Am J Physiol,2004; 287(3):H1179-H1185.
[4]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[5]Thorburn J, Frost JA, Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy [J]. J Cell Biol,1994; 126(6):1565-1572.
[6]Widmann C, Gibson S, Jarpe MB, et al. Mitogen-activated protein kinase: Congservation of a three-kinase module from yeast to human [J]. Physiol Rev, 1999; 79(1):143-180.
[7]吴彬,胡胜娣,潘慧,等.可卡因-苯丙胺调节转录肽激活ERK促进海马神经元合成BDNF [J].中国病理生理杂志,2007；23(7)：1289-1292.
[8]王祥,戴友平,杨杪,等.心房颤动心房组织内细胞外信号调节激酶和血管紧张素转化酶表达的研究[J].中华心血管病杂志,2004；32(3)：207-210.
[9]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[10]Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases [J]. Science,2002; 298(5600):1911-1912.
[11]Okuno S, Saito A, Hayashi T, et al. The c-Jun N-terminal protein kinase signalling pathway mediates Bax activation and subsequent neumnal apoptosis through interaction with Bim after transient focal cerebral ischemia [J]. J Neumsci,2004; 24(36):7879-7887.
[12]Chappell WH, Steelman LS, Long JM, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors:rationale and importance to inhibiting these pathways in human health [J]. Oncotarget,2011; 2(3):135-164.
[13]Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs [J]. Oncogene,2007; 26(22):3100-3112.
[14]Zhang W, Lee JC, Kumar S, et al. ERK pathway mediates the activation of Cdk2 in IGF-1-induced proliferation of human osteosarcoma MG-63 cells [J]. JBone Miner Res,1999; 14(4):528-535.
[15]Tang DM, Wu DC, Hirao A, et al. ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53 [J]. JBiol Chem,2002; 277(15):12710-12717.
[16]Black EJ, Walker M, Clark W, et al. Cell transformation by v-Jun deactivates ERK MAP kinase signaling [J]. Oncogene,2002; 21(42):6540-6548.
[17]Kamio N, Akifusa S, Yamagnchi N, et al. Induction of granulocyte colony-stimulating factor by globular adiponectin via the MEK-ERK pathway [J]. Molecular and Cellular Endocrinology,2008; 292(1-2):20-25.
[18]Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome [J]. Science,2002; 298(5600):1912-1934.
[19]Chambard JC, Renaud L, Pouyssegur J, et al. ERK implication in cell cycle regulation [J]. Biochim Biophys Acta.,2007; 1773(8):1299-1310.
[20]Rajalingam K, Rudel T. Ras-Raf signaling needs prohibitin [J]. Cell Cycle,2005; 4(11):1503-1505.
[21]Robertson JD, Zhivotovsky B. Orrenius S. Review:nuclear events in apoptosis [J]. J Struct Biol,2000; 129(2-3):346-358.
[22]Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer [J]. Oncogene,2007; 26(22): 3291-3310.
[23]McCubrey JA, May S, Duronio V, et al. Serine/threonine phosphorylation in cytokine signal transduction [J]. Lerkemia,2000; 14(1):9-21.
[24]Arbabi S, Maier RV. Mitogen-activated protein kinase [J]. Crit CareMed,2002; 30:874-879.
[25]John M, Kyriakis. The integration of signaling by multiprotein complexes containing Raf kinase [J]. Biochim Biophys Acta,2007; 1773(8):1238-1247.
[26]Yamamoto T, Cui XM, Shuler CF. Role of ERK1/2 signaling during EGF-induced inhibition of palatal fusion [J]. Dev Bio,2003; 260(2):512-521.
[27]Sabio G, Reuver S, Feijoo C, et al. Stress and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38y and ERK1/ERK2 [J]. Biochemical Journal,2004; 380(Pt 1):19-30.
[28]Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1 [J].Adv Pharmacol,2010; 60:1-26.
[29]Min LJ, Mogi M, Iwai M, et al. Signaling mechanisms of angiotensin Ⅱ in regulating vascular senescence [J]. Ageing Res Rev,2009; 8(2):113-121.
[30]Franco M, P e rez-Mend e z O, Martinez F. Interaction of intrarenal adenosine and angiotensin Ⅱ in kidney vascular resistance [J]. Curr Opin Nephrol Hypertens, 2009; 18(1):63-67.
[31]Li J, Li J, Liang F, et al. Electroacupuncture at PC6 (Neiguan) Improves Extracellular Signal-Regulated Kinase Signaling Pathways Through the Regulation of Neuroendocrine Cytokines in Myocardial Hypertrophic Rats [J]. Evid Based Complement Alternat Med. doi:10.1155/2012/792820.
[1]王华主编.《针灸学》.高等教育出版社,2008：184.
[2]石学敏.针灸学[M].北京：中国中医药出版社,2007：195.
[3]严振国.经穴断面解剖图谱[M].上海：上海科学技术出版社,2002：58.
[4]文琛.人的小血管壁神经分布及其与经络气血的关系[J].中国针灸,1981；2：282.
[5]沈雪勇,党瑞山,陈尔瑜,等.胃经腧穴与结缔组织结构和钙元富集关系[J].中国针灸,1998；18(10)：595-596.
[6]张静.针刺厥阴俞、心俞与T4-T5夹脊穴对缺血性心脏病患者心电图即刻效应的对比观察[D].山东中医药大学,2008年.
[7]Lorell BH, Carabello BA. Left ventricular hypertrophy:pathogenesis, detection, and prognosis [J]. Circulation,2000; 102(4):470-479.
[8]Nakagami H, Takemoto M, Liao JK. NADPH oxidase-derived superoxide anion mediates angiotensin Ⅱ-induced cardiac hypertrophy [J]. J Mol Cell Cardio,2003; 35(7):851-859.
[9]Johnson JA. An epsilonPKC-selective inhibitor attenuates back phosphorylation of a low molecular weight protein in cardiac myocytes [J]. Cell Signal,2003; 15(11):123-130.
[10]Russell B, Motlagh D, Ashley WW. Form follows function:how muscle shape is regulated by work [J]. J Appl Physiol,2000; 88(3):1127-1132.
[11]Ozaki M, Kawashima S, Yamashita T, et al. Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion [J]. Circ J,2002; 66(9):851-856.
[12]Toriis, Nakayama K, Yamamoto T, et al. Regulatory mechanisms function of ERK MAP kinases [J]. J Riochem,2004; 136(5):557-561.
[13]Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer [J]. Nat Rev Cancer.2004; 4(12):937-947.
[14]Thorburn J, Frost JA, Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy [J]. J Cell Biol,1994; 126(6):1565-1572.
[15]Bonni A, Brunet A, West A E, et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms [J]. Science,1999; 286(5443):1358-1362.
[16]Haq S, Choukroun G, Lim H, et al. Molkentin JD. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure [J]. Circulation,2001; 103(5):670-677.
[17]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[18]Wang L, Proud CG Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes [J]. Circ. Res,2002; 91(9):821-829.
[19]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-repeffusion injury by inhibiting events in the early minutes of reperfusian [J]. Cardiovnsc Res.2004; 62(1):74-85.
[20]Sun HY, Wang NP, Kerendi F, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol,2005; 288(4):H1900-1908.
[21]吴刚,杨蕾,刘永锋,等.缺血预处理对大鼠肝脏缺血再灌注损伤保护作用机制的研究[J].中华肝胆外科杂志,2003；9(4)：221-224.
[22]Alvarez-Jaimes L, Feliciano-Rivera M, Centeno-Gonzalez M, et al. Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens [J]. J Pharmacol Exp Ther,2005; 314(3):1144-1157.
[23]Lips D J, Bueno O F, Wilkins B J, et al. MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo [J]. Circulation,2004; 109(16): 1938-1941.
[24]Bhatt R R, Jr Ferrell J E. The protein kinase p90 rsk as an essential mediator of cytostatic factor activity [J]. Science,1999; 286(5443):1362-1365.
[25]Baines C P, Zhang J, Wang G W, et al. Mitochondrial PKC epsilon and MAPK form signaling modules in the murine heart:enhanced mitochondrial PKC epsilon-MAPK interactions and differential MAPK activation in PKC epsilon-induced cardioprotection [J]. Circ Res,2002; 90(4):390-397.
[26]Gorin Y, Ricono JM, Wagner B. Angiotensin Ⅱ-induced ERK1/2 activation and protein synthesis are redox-dependent in glomerular mesangial cells [J]. Biochem, 2004; 381(1):231-239.
[27]王智刚,张卫泽,马凌,等.抑制ERK1/2通路激活改善大鼠心房纤维化和缝隙连接蛋白40重构[J].第二军医大学学报,2012；33(3)：259-264.
[28]Merrill WH, Friesinger GC, Graham TP Jr, et al. Long-lasting improvement after septal myectomy for hypertrophic obstructive cardiomyopathy [J]. Ann Thorac Surg,2000; 69(6):1732-1735.
[29]Ritchie RH, Irvine JC, Rosenkranz AC, et al. Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy:NON and beyond [J]. Pharmacol Ther,2009; 124(3):279-300.
[30]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[31]Ocaranra M P, Diaz Araya G, Chiong M, et al. Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis [J]. J Cardiovase Pharmacol,2002; 41(2):1246-1254.
[32]Stanton HC, Brenner G, Mayfield ED Jr. Studies on isoproterenol induced cardiomegaly in rats [J]. Am Heart J,1969; 77(1):72-80.
[33]Borges JC, Silva JA Jr, Gomes MA, et al. Tonin in rat heart with experimental hypertrophy [J]. Am J Physiol Heart Circ Physiol,2003; 284(6):2263-2268.
[34]CAM FS, RAY M. Hypertrophic cardiomyopathy:pathological features and molecular pathogenesis [J]. Anadolu Kardiyol Derg,2004; 4(4):327-330.
[1]Ma KW:Acupuncture:Its place in the history of Chinese medicine. Acupunct Med 2000;18:88-99.
[2]Middlekauff HR. Acupuncture in the treatment of heart failure. Cardiol Rev 2004;12(3):171-3.
[3]Schoen AM. Veterinary acupuncture:ancient art to modern medicine. St. Louis, Missouri, U.S.A:Mosby, Inc 2001;19-23:127-48.
[4]Tam KC, Yiu HH. The effect of acupuncture on essential hypertension. Am J Chin Med 1975;3(4):369-75.
[5]Richter A, Herlitz J, Hjalmarson A. Effect of acupuncture in patients with angina pectoris. Eur Heart J 1991; 12(2):175-8.
[6]NIH Consensus Conference. Acupuncture. JAMA 1998;280(17):1518-24.
[7]Ballegaard S, Jensen G, Pedersen F, et al. Acupuncture in severe, stable angina pectoris:a randomized trial. Acta Med Scand 1986;220(4):307-13.
[8]Gao ZW, Yu XZ, Shen AX, et al. Clinical observations on treatment of 220 cases of arrhythmia with acupuncture. Compilation of the abstract of acupuncture and moxibustion papers (Abstract). The First World Conference on Acupuncture-Moxibustion 1987;13-4.
[9]Li P, Tjen-ALooi SC, Longhurst JC. Excitatory projections from arcuate nucleus to ventrolateral periaqueductal gray in electroacupuncture inhibition of cardiovascular reflexes. Am J Physiol Heart Circ Physiol 2006;290(6):2535-42.
[10]Tjen-A-Looi SC, Li P, Longhurst JC. Midbrain vIPAG inhibits rVLM cardiovascular sympathoexcitatory responses during acupuncture. Am J Physiol Heart Circ Physiol 2006;290(6):2543-53.
[11]Tjen-A-Looi SC, Li P, Longhurst JC. Role of medullary GABA, opioids, and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electroacupuncture in cats. Am J Physiol Heart Circ Physiol 2007;293(6):3627-35.
[12]Tsou MT, Ho JY, Lin CH, et al. Proteomic analysis finds different myocardial protective mechanisms for median nerve stimulation by electroacupuncture and by local somatothermal stimulation. Int JMol Med 2004;14(4):553-63.
[13]Li P. Neural mechanisms of the effect of acupuncture on cardiovascular diseases. Satellite Symposium of 34th world congress of the International Union of Physiological Sciences (IUPS), Electroacupuncture:is there a physiological basis? Auckland, New Zealand, pp 5, International Congress Sciences 2002; 1238:71-7.
[14]Li P, Pitsillides KF, Rendig SV, et al. Reversal of reflex-induced myocardial ischemia by median nerve stimulation:a feline model of electroacupuncture. Circulation 1998;97(12):1186-94.
[15]Crisostomo M, Li P, Tjen-A-Looi SC, et al. Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats. JAppl Physiol 2005;98(6):2056-63.
[16]Lin JH, Shih CH, Kaphle K, et al. Acupuncture effects on cardiac functions measured by cardiac magnetic resonance imaging in a feline model. Evid Based Complement Alternat Med 2010;7(2):169-76.
[17]Napadow V, Dhond RP, Purdon P, et al. Correlating acupuncture FMRI in the human brainstem with heart rate variability. Conf Proc IEEE Eng Med Biol Soc 2005;5:4496-9.
[18]Li P, Tjen-A-Looi SC, Guo ZL, et al. Long-loop pathways in cardiovascular electroacupuncture responses. JAppl Physiol 2009;106(2):620-30.
[19]Tjen-A-Looi SC, Li P, Longhurst JC. Processing cardiovascular information in the vlPAG during electroacupuncture in rats:roles of endocannabinoids and GABA. JAppl Physiol 2009; 106(6):1793-9.
[20]Fu LW, Longhurst JC. Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 2009;106(6): 1800-9.
[21]Sakatani K, Kitagawa T, Aoyama N, et al. Effects of acupuncture on autonomic nervous function and prefrontal cortex activity. Adv Exp Med Biol 2010;662: 455-60.
[22]Chang S, Chao WL, Chiang MJ, et al. Effects of acupuncture at Neiguan (PC6) of the pericardial meridian on blood pressure and heart rate variability. Chin J Physiol 2008;51(3):167-77.
[23]Li JS, Yan J, He JF, et al. Effects of electroacupuncture on c-fos expression in nucleus of the solitary tract and electrocardiogram ST (II) in myocardial ischemia rats. Zhen Ci Yan Jiu 2009;34(3):171-4.
[24]Chao DM, Shen LL, Tjen-A-Looi S, et al, Naloxone reverses inhibitory effect of electroacupuncture on sympathetic cardiovascular reflex responses. Am J Physiol 1999;276:2127-34.
[25]Tjen-ALooi SC, Li P, Longhurst JC. Prolonged inhibition of rostral ventral lateral medullary premotor sympathetic neuron by electroacupuncture in cats. Auton Neurosci 2003; 106:119-31.
[26]Zhou W, Fu LW, Guo ZL, et al. Role of glutamate in rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation. Am J Physiol Heart Circ Physiol 2007;292(4):1868-75.
[27]Li P, Tjen-A-Looi SC, Guo ZL, et al. An arcuate-ventrolateral periaqueductal gray reciprocal circuit participates in electroacupuncture cardiovascular inhibition. Auton Neurosci 2010;158(1-2):13-23.
[28]Holaday JW. Cardiovascular effects of endogenous opiate systems. Am J Physiol 1983;276:2127-34.
[29]Jin Y, Cao Q, Zhuang D. Function of nucleus of solitary tract in the correlation between heart and acupoint Neiguan. J Trad Chin Med 1988;8:61-8.
[30]Li P, Tjen-A-Looi S, Longhurst JC. Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic responses in cats. Auton Neurosci 2001;89(1-2):38-47.
[31]Moazzami A, Tjen-A-Looi SC, Guo ZL, et al. Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture. JAppl Physiol 2010;108(5):1336-46.
[32]Zhi-Ling Guo, Ali R. Moazzami, Stephanie Tjen-A-Looi, et al. Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture. Brain Res 2008; 1229:125-36.
[33]Coleman MJ, Dampney RA. Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus. Am J Physiol 1995;268:1295-302.
[34]Bago M, Marson L, Dean C. Serotonergic projections to the rostroventrolateral medulla from midbrain and raphe nuclei. Brain Res 2002;945:249-58.
[35]Orer HS, Gebber GL, Barman SM. Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm. Am J Physiol 2008;294:1435-44.
[36]Takayama S, Seki T, Watanabe M, et al. Brief effect of acupuncture on the peripheral arterial system of the upper limb and systemic hemodynamics in humans. JAltern Complement Med 2010;16(7):707-13.
[37]Hunt SP, Lovick TA. The distribution of serotonin, met-enkephalin and beta-lipotropin-like immunoreactivity in neuronal perikarya of the cat brainstem. NeurosciLett 1982;30:139-45.
[38]Arvidsson U, Cullheim S, Ulfhake B, et al. Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem. Synapse 1992;11:85-104.
[39]Krukoff TL. Central actions of nitric oxide in regulation of autonomic functions. Brain Res Rev 1999;30:52-65.
[40]Tjen-A-Looi SC, Phan NT, Longhurst JC. Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin. Am J Physiol Heart Circ Physiol 2001;281(5):2010-7.
[41]Wang J, Chen ZJ, Luo CQ, et al. The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip goldblatt hypertension rat. Acta Physiol Sin 2002;54(2):175-8.
[42]Guo ZL, Longhurst JC. Activation of nitric oxide-producing neurons in the brain stem during cardiac sympathoexcitatory reflexes in the cat. Neuroscience 2003;116(1):167-78.
[43]Wang C, Tian YF, Zhou D, et al. Influence of electroacupuncture on myocardial NO and NOS and intracellular Ca2+ contents in myocardial ischemia-reperfusion injury rats. Zhen Ci Yan Jiu 2010;35(2):113-7.
[44]Zhong H, Li GZ. Study on the mechanism of electroacupuncture of "Neiguan" (PC 6) in inhibiting ventricular arrhythmia induced by hypothalamic electrostimulation in the rabbit. Zhen Ci Yan Jiu 2009;34(11):43-7.
[45]World Health Organization. Guidelines for clinical research in acupuncture. Western Pacific series no.15. Manila, Philippines:WHO Regional Office for the Western Pacific,1995.
[46]Jo HG, Jo GH. Electroencephalogram activity induced by magnetic stimulation on heart meridian. Neurosci Lett 2011.
[47]Zhou Yi Syuu W, Hsiao I, Lin VW, et al. Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation:role of the spinal cord. J Appl Physiol 2006;100(3):926-32.
[2]周凤梧,张奇文,丛林.名老中医之路[M].济南：山东科学技术出版社,2005：181.
[3]Kuusisto J, Karja V, Sipola P, et al. Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy [J]. Heart.2012 Mar 24. [Epub ahead of print]
[4]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[5]Izzo JL Jr, Gradman AH. Machanisms and management of hypertensive heart disease:from left ventrie hypertrophy to heart failure [J]. Med Clin North Am, 2004; 88 (5):1257-1271.
[6]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-repeffusion injury by inhibiting events in the early minutes of reperfusian [J]. Cardiovasc Res.2004; 62(1):74-85.
[7]Sun HY, Wang NP, Kerendi F, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+overload [J]. Am J Physiol Heart Circ Physiol,2005; 288(4):H1900-1908.
[8]吴刚,杨蕾,刘永锋,等.缺血预处理对大鼠肝脏缺血再灌注损伤保护作用机制的研究[J].中华肝胆外科杂志,2003；9(4)：221-224.
[9]Alvarez-Jaimes L, Feliciano-Rivera M, Centeno-Gonzalez M, et al. Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens [J]. J Pharmacol Exp Ther 2005; 314(3):1144-1157.
[10]Bonni A, Brunet A,West A E, et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms [J]. Science,1999; 286(5443):1358-1362.
[11]Haq S, Choukroun G, Lim H, et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure [J]. Circulation,2001; 103(5):670-677.
[12]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[13]Wang L, Proud CG. Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes [J]. Circ. Res,2002; 91(9):821-829.
[14]王祥,戴友平,杨杪,等.心房颤动心房组织内细胞外信号调节激酶和血管紧张素转化酶表达的研究[J].中华心血管病杂志,2004；32(3)：207-210.
[15]王春雷,王升旭,龚伟.佐剂关节炎大鼠脊髓背角内磷酸化ERK在电针夹脊穴镇痛中的变化[J].上海针灸杂志,2005；24(12)：33-35.
[16]姜雪梅,原林,张学全,等.针刺对大鼠局部筋膜和脊髓细胞外信号调节激酶1/2和P38丝裂酶原活化蛋白激酶信号通路的影响[J].中国康复医学杂志,2009；24(11)：973-976.
[17]Guan X, Wu HG, Ma XP, et al. Experimental Research of Electroacupuncture on ERK Phosphorylation in Rats of Hepatofibrosis [J]. J Acupunct. Tuina. Sci,2009; 5(7):270-273.
[18]张威,马贤德,王健.眼针对脑缺血再灌注模型大鼠ERK1/2信号转导通路影响的实验研究[J].中国医科大学学报,2012；41(1)：42-44.
[19]尤行宏,陈泽斌,王华,等.内阿片肽在“双固一通”针法保护缺血心肌中的作用[J].中国老年学杂志,2010；12(30)：3686-3688.
[20]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠肥厚心肌病理组织学影响的研究[J].世界中西医结合杂志,2008；3(6)：319-321.
[21]王华,喻建兵,吴绪平,等.电针郄门穴对室性心动过速模型大鼠心率及血浆一氧化氮含量的影响[J].2010；51(9)：814-816.
[22]吴松,唐宏图,陈泽斌,等.“双固一通”针法对急性心肌缺血模型大鼠心肌组织过氧化物酶活性的影响[J].湖北中医杂志,2006；28(10)：3-5.
[23]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠心肌SOD、GSH-PX活性和MDA含量的影响[J].湖北中医学院学报,2006；8(2)：15-16.
[24]尤行宏,王华,陈泽斌,等.延髓内阿片肽对电针抗心肌缺血效应的影响,现代中西医结合杂志[J].2009；18(29)：3541-3544.
[25]李明磊,王华,陈泽斌.电针内关穴对AMI大鼠自主神经与中枢P物质、一氧化氮合酶的影响[J].中华中医药杂志,2007；22(8)：543-546.
[26]王华,邓丽霞,吴绪平,等.电针“内关”对室性心动过速大鼠心率及血浆儿茶酚胺含量的影响[J].针刺研究,2009；34(3)：180-182.
[27]洪亚群,王华.“双固一通”针法对甲亢性心肌病大鼠Ang Ⅱ、ET及CGRP的影响[J].中国康复,2008；23(3)：150-151.
[28]Radzievsky SA, Lebedeva OD, Fisenko LA, et al. Function of myocardial contraction and relaxation in essential hypertension in dynamics of acupuncture therapy [J]. Am J Chin Med,1989; 17(3-4):111-117.
[1]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocyte hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[2]Yin W, Zhang P, Huang JH, et al. Stimulation of kappa-opioid receptor reduces isoprenaline-induced cardiac hypertrophy and fibrosis [J]. Eur J Pharmacol,2009; 607(1-3):135-142.
[3]Kitagawa Y, Yamashita D, Ito H, et al. Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts [J]. Am J Physiol Heart Circ Physiol,2004; 287(1):H277-H285.
[4]Bos R, Mougenot N, Findj i L, et al. Inhibition of catecholamine-induced cardiac fibrosis by an aldosterone antagonist [J]. Cardiovasc Pharmacol,2005; 45(1): 8-13.
[5]Li L, Zhang LK, Pang YZ, et al. Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury 38induced by isoproterenol in rats [J]. Acta Pharmacol Sin,2006; 27(5):527-535.
[6]沈楠,王艳春,范红艳,等.异丙肾上腺素致大鼠心肌肥厚及对相关因子的影响[J].吉林医药学院学报,2007；28(3)：141-143.
[7]Tang XD, Zhou X, Zhou KY. Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor lalpha protein accumulation and vascular endothelial growth factor expression in human breast cancer cells [J]. Acta Pharmacol Sin,2009; 30(5):605-616.
[8]Kui L, Weiwei Z, Ling L, et al. Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway [J]. Regul Pept,2009; 155(1-3):62-69.
[9]Alessi DR, Cuenda A, Cohen P, et al. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo [J]. J Biol Chem,1995; 270(46):27489-27494.
[10]Zheng JJ, Chen C, Wang G, et al. Effect of MEK1 inhibitor PD98059 on the signal transduction of Tec in HepG2 hepatoma cells [J]. Chinese-German Journal of Clinical Oncology,2007; 6(6):542-545.
[11]吴珍,李胜保,童强.PD98059对食管癌细胞放射敏感性影响的研究[J].临床消化病杂志,2009；21(4)：198-200.
[12]Hsu CC, Weng CS, Liu TS, et al. Effects of electrical acupuncture on acupoint BL15 evaluated in terms of heart rate variability, pulse rate variability and skin conductance response [J]. Am J Chin Med,2006; 34(1):23-36.
[13]Zhou W, Fu LW, Tjen-A-Looi SC, et al. Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses [J]. J Appl Physiol,2005; 98(3):872-880.
[14]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[15]昊钟琪,赵祥文.现代诊疗新技术,长沙：湖南科学技术出版社[M].1987：249-252.
[16]Boluyt M O, Long X, Eschenhagen T, et al. Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart [J]. Am J Physiol Heart Circ Physiol,1995; 269(2 Pt 2):H638-H647.
[17]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocite hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[18]Ivens E. Hypertrophic cardiomyopathy. Heart Lung Circ,2004; 13 Suppl 3: S48-55.
[19]Mann DL. Inflammatory mediators and the failing heart:past, present and the foreseeable future [J]. Circ Res,2002; 91(11):988-998.
[20]Nian M, Lee P, Khaper N, et al. Inflammatory cytokines and postmyocardial infarction remodeling [J]. Circ Res,2004; 94(12):1543-1553.
[21]Aukrust P, Gullestad L, Ueland T, et al. Inflammatory and anti-inflammatory cytokines in chronic heart failure:potential therapeutic implications [J]. Ann Med, 2005; 37(2):74-85.
[22]陈亦人.伤寒论译释[M].上海：上海科学技术出版社,1 992：11-12.
[23]罗明富,王平,刘俊岭,等.电针“内关”穴对家兔急性心肌缺血区肌原纤维、线粒体和血小板的影响[J].针刺研究,2001；26(2)：119-121.
[24]田岳风,严洁,林亚平,等.电针“内关”对心肌缺血再灌注损伤内皮素及超微结构的影响[J].中国针灸,2002；22(8)：547-549.
[1]Shimizu M, Ino H, Yamagychi M, et al. Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin I mutation [J]. Am Heart J,2001; 143(2):289-293.
[2]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[3]黄宛.主编临床心电图学[M]：第5版,北京：人民卫生出版社,2001：23-41.
[4]Kralova E, Mokran T, Murin J, et al. Electrocardiography in two model s of isoproterenol-induced left ventricular remodeling [J]. Physiol Res,2008; (Suppl.2):S83-S89.
[5]Boluyt M O, Long X, Eschenhagen T, et al. Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart [J]. Am J Physiol Heart Circ Physiol,1995; 269(2 Pt 2):H638-H647.
[6]Wollert KC, Drexler H. Regulation of cardiac remodeling by nitric oxide:focus on cardiac myocyte hypertrophy mad apoptosis [J]. Heart Fail Rev,2002; 7(4): 317-325.
[7]CAM FS, RAY M. Hypertrophic cardiomyopathy:pathological features and molecular pathogenesis [J]. Anadolu Kardiyol Derg,2004; 4(4):327-330.
[8]严洁,刁利红,易受乡,等.电针内关穴对心肌缺血再灌注损伤大鼠心肌能量代谢及组织形态学的影响[J].中国组织工程研究与临床康复,2007；11(47)：9443-9447.
[9]Kim E, Cho JH, Jung WS, et al. Effect of acupuncture on heart rate variability in primary dysmenorrheic women [J]. Am J Chin Med,2011; 39(2):243-249.
[10]Li Z, Wang C, Mak AF, et al. Effects of acupuncture on heart rate variability in normal subjects under fatigue and non-fatigue state [J]. Eur J Appl Physiol,2005; 94(5-6):633-640.
[11]徐俊华,施苗吾,胡丽霞.针刺合谷穴治疗心绞痛初探[J].上海针灸杂志,1993,12(3)：101.
[12]李颖文,刘东生,符文彬.针灸从“四关”穴论治及其临床应用-跟符文彬主任学习心得[A].广东省针灸学会第九次学术交流会论文汇编[C].2004.
[13]林仁勇,吴俊贤,张佩,等.神门穴真、假针刺对心率和心率变异性影响的比较研究[J].时珍国医国药,2012；23(3)：752-754.
[14]林仁勇,陈俊琦,吴秋萍,等.针刺神门穴对心率变异性频域指标影响的研究[J].新中医,2010；42(10)：95-96.
[15]陈俊琦,廖韩波,王娇,等.针刺神门穴与非穴对心率及心率变异性影响的比较研究[J].针刺研究,2011；17(11)：1248-1249.
[16]刘丽芝,陈俊琦,吴秋萍,等.基于心率变异性分析针刺神门穴影响心率的机制[J].针灸临床杂志,2010；26(6)：45-46.
[17]林冬群,林宇,胡佳,等.电针内关、神门穴对冠心病冠脉旁路移植术后心功能的影响[J].现代中西医结合杂志,2009,18(19)：2241-2242.
[18]程斌,谭奇纹.电针对冠心病患者心电图即刻效应的对比观察[J].上海针灸杂志,2008,27(5)：12-14.
[19]周美启,高纺,吴生兵,等.针刺心包经、心经对急性心肌缺血模型大鼠心肌肌钙蛋白T的影响[J].中医药临床杂志,2011；23(11)：951-952.
[20]高纺,吴生兵,曹健,等.针刺心经心包经对急性心肌缺血大鼠心电图J点、T波振幅及心肌梗死面积的影响[J].安徽中医学院学报,2011；30(5)：53-56.
[1]Sunoda M. Role of catecholamine metabolism in blood pressure regulation using chemiluminescence reaction detection [J]. Yakugaku Zasshi,2008; 128(11): 1589-1594.
[2]裴兆辉,朱妙章,裴建明,等.高效液相色谱测定大鼠血浆儿茶酚胺的含量[J].心脏杂志,2003；15(1)：9-11.
[3]Shida M. Role of adrenergic receptor system in canine left ventricular hypertrophy [J]. Kokyu To Junkan,1989; 37(3):321-327.
[4]Cohen J. Role of endocrine factors in the pathogenesis of cardiac hypertrophy [J]. Circ Res,1974; 35(2):supplⅡ:49-57.
[5]Walker DM. Update on epinephrine (adrenaline) for pediatric emergencies [J]. Curr Opin Pediatr,2009; 21(3):313-319.
[6]Prasad AA, Pasterkamp RJ. Axon guidance in the dopamine system [J]. Adv Exp Med Biol,2009; 651:91-100.
[7]Cave JW, Baker H. Dopamine systems in the forebrain [J]. Adv Exp Med Biol, 2009; 651:15-35.
[8]Schindler CW, Karcz-Kubicha M, Thorndike EB, et al. Lack of adenosine Al and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A2A receptor agonist CGS 21680[J]. Eur J Pharmacol,2004; 484(2-3): 269-275.
[9]Hurst RS, Higdon NR, Lawson JA, et al. Dopamine receptor agonists differ in their actions on cardiac ion channels [J]. Eur J Pharmacol,2003; 482 (1-3):31-37.
[10]李佳,刘建民,刘溪泉,等.电针“强壮”穴对亚急性衰老大鼠神经免疫调节的影响[J].中国针灸,2009；29(11)：905-909.
[11]王华,邓丽霞,吴绪平,等.电针“内关”对室性心动过速大鼠心率及血浆儿茶酚胺含量的影响[J].针刺研究,2009；34(3)：180-182.
[12]王祥瑞,王震虹,林函,等.电针刺对缺血再灌注后心肌的保护作用[J].中国药物与临床,2005；5(5)：328-331.
[13]Uchida S, Shimura M, Ohsawa H, Suzuki A. Neural mechanism of bradycardiac responses elicited by acupuncture-like stimulation to a hind limb in anesthetized rats [J]. J Physiol Sci,2007; 57(6):377-382.
[1]Velez Rueda JO, Palomeque J, Mattiazzi A. Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII [J]. J Appl Physiol.2012 Apr 5. PMID:22492934 [Epub ahead of print].
[2]何建桂,黄艺仪,马虹,等.血管紧张素-(1-7)对心肌肥厚的影响及其与细胞外信号调节激酶的关系[J].中国病理生理杂志,2005；21(9)：1713-1716.
[3]姜庆军,徐耕,朱有法.伊贝沙坦和培垛普利对大鼠压力负荷性心肌肥厚的影响[J].中国病理生理杂志,2004；20(5)：827-831.
[4]Dstal D.E, Baker K.M. The cardiac rennin-angiotensin system:conceptual, or a regulator of cardiac function [J]. nCric Res,1999; 85:643-650.
[5]Pelouch V, Kolar F, O stadal B, et al.Regression of chronic hypoxia-induced pulmonary hypertension, pulmonary hypertension, right ventricular hypertrophy, and fibrosis:effect of Enalapriln [J]. Cardiovase Drug Ther,1997; 11(2):177-185.
[6]Golomb E, Abassi Z A, Cude G, et al. Angiotensin 1I maintains, but does not mediate.isoproterenol-induced cardiac hypertrophy in rats [J]. Am J Physiol,1994; 267(4):1496-1506.
[7]秦旭平,龙光,徐立朋,等.氯沙坦和培垛普利逆转高血压大鼠心血管重构 的比较[J].中国药理学通报,2004；20(10)：1107-1111.
[8]Borges JC, Silva JA J r, Gomes MA, et al. Tonin in rat heart with experimental hypertrophy [J]. Am J Physiol Heart Circ Physiol,2003; 284 (6):H2263-2268.
[9]Lorell BH. Role of angiotensin AT1 and AT2 receptors in cardiac hyper trophy and disease [J]. Am J Cardiol,1999; 83(12A):48-52.
[10]Motoaki Sano, Keiichi Fukuda, Toshiniko Sato. ERK and p38MAPK, but not NF-κB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin Ⅱ in cardiac fibroblasts [J]. CircRes,2001; 89(8):661.
[11]Henry E Kim, Seema S Dalal, Erik Young.Disruption of the myocardial extracellular matrix leads to cardiac dysfunction [J]. J Clin Invest,2000; 106(7): 857.
[12]George W Booz, Jonathan N E Day, Kenneth M Baker.I nterplay between the cardiac rennin angiotensin system and JAK-STAT signaling:role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure [J]. J Mol Cell Cardiol,2002; 34(11):1443.
[13]梁敏,林赛娟,梁宁.乌拉地尔对高血压患者血浆4种神经肽含量的影响[J].中华麻醉学杂志,2000；20：24-25.
[14]Mancia GA, White WB. In white coat hypertension innocent or detrimental [J]. Blood Press Monit,1999; 4(5):241-247.
[15]Bass C, Thiene G, Della Barbera M, et al. Endothelin A receptor antagonist administration immediately after experimental myocardial infaretion with reperfusion does not affect scar healing in dogs [J]. Cardiovascnlar research,2002; 55(1):113-121.
[16]Clozel M, Qiu C, Hess P, et al. Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction [J]. J Am Col Cardiol,2002; 239(1):142-147.
[17]Aqnetti G, Bezstarosti k, et al. Proteomic profiling of endothelin-1 stimulated hypertrophic cardiomyoeytes reveals the increase of four different desmin species and alpha-B-crystallin [J].2008; 1784(7-8):1068-107.
[18]Piuhola J, Szokodi I, Kinnunen P, et al. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts [J]. Hypertension,2003; 41(1): 93-99.
[19]You H W, Chen X, You H J, et al. Role of endothelin-1 and its receptors on hypertrophy or proliferation of cultured cardial cells [J]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao,2006; 28(4):520-523.
[20]孔令雷,颜玲娣,宫泽辉.内皮素系统与心肌肥厚[J].中国药理学通报,2008；24(9)：1127-1130.
[21]Choi SR, Jang JS, Lee JH, et al. Role of serum tumor markes in monitoring for recurrence of gastric cancer following radical gastrectomy [J]. Dig Dis Sci,2006; 51(11):2081-2086.
[22]Dohiy, Hahn AW, Boulanger CM, et al. Endothelin stimulated by angiotensin angiotensin contractility of spontaneously hypertensive rat resistance arteries [J]. Hypertension,1992; 19(2):131-137.
[23]DUscio LV, Barton M, Shaw S, et al. Structure and function of small arteries in salt-induced hypertension:effects of chronic endothelin-subtype-A-receptor blockade [J]. Hypertension,1997; 30(4):905-911.
[24]Oriji GK, Keiser HR. Protein Kinase C mediates angiotensin-induced contractions and the release of endothelin and prostacyclin in rat aortic rings. Prostag landins leukotrienes [J]. Essential Fatty Acids,1997; 57(2):135-141.
[25]Luscher TF. Endothelial dysfunction:the role and impact of the rennin angiotensin system [J]. Heart,2000; 84(1):i20-22.
[26]Ruiz-Opazo N, Hirayama K, et al. Molcecular characterization of a dual endothelin-1/Angiotensin Ⅱ receptor. Mol Med,1998; 4(2):96-108.
[1]Ritchie RH, Irvine JC, Rosenkranz AC, et al. Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy:NON and beyond [J]. Pharmacol Ther,2009; 124(3):279-300.
[2]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[3]Ritchie RH, Rosenkranz AC, Huynh LP, et al. Activation of IP prostanoid receptors prevents cardiomyocyte hypertrophy via cAMP-dependent signaling [J]. Am J Physiol,2004; 287(3):H1179-H1185.
[4]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[5]Thorburn J, Frost JA, Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy [J]. J Cell Biol,1994; 126(6):1565-1572.
[6]Widmann C, Gibson S, Jarpe MB, et al. Mitogen-activated protein kinase: Congservation of a three-kinase module from yeast to human [J]. Physiol Rev, 1999; 79(1):143-180.
[7]吴彬,胡胜娣,潘慧,等.可卡因-苯丙胺调节转录肽激活ERK促进海马神经元合成BDNF [J].中国病理生理杂志,2007；23(7)：1289-1292.
[8]王祥,戴友平,杨杪,等.心房颤动心房组织内细胞外信号调节激酶和血管紧张素转化酶表达的研究[J].中华心血管病杂志,2004；32(3)：207-210.
[9]李志勇,孙建宁,张硕峰.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008；27(2)：299-302.
[10]Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases [J]. Science,2002; 298(5600):1911-1912.
[11]Okuno S, Saito A, Hayashi T, et al. The c-Jun N-terminal protein kinase signalling pathway mediates Bax activation and subsequent neumnal apoptosis through interaction with Bim after transient focal cerebral ischemia [J]. J Neumsci,2004; 24(36):7879-7887.
[12]Chappell WH, Steelman LS, Long JM, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors:rationale and importance to inhibiting these pathways in human health [J]. Oncotarget,2011; 2(3):135-164.
[13]Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs [J]. Oncogene,2007; 26(22):3100-3112.
[14]Zhang W, Lee JC, Kumar S, et al. ERK pathway mediates the activation of Cdk2 in IGF-1-induced proliferation of human osteosarcoma MG-63 cells [J]. JBone Miner Res,1999; 14(4):528-535.
[15]Tang DM, Wu DC, Hirao A, et al. ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53 [J]. JBiol Chem,2002; 277(15):12710-12717.
[16]Black EJ, Walker M, Clark W, et al. Cell transformation by v-Jun deactivates ERK MAP kinase signaling [J]. Oncogene,2002; 21(42):6540-6548.
[17]Kamio N, Akifusa S, Yamagnchi N, et al. Induction of granulocyte colony-stimulating factor by globular adiponectin via the MEK-ERK pathway [J]. Molecular and Cellular Endocrinology,2008; 292(1-2):20-25.
[18]Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome [J]. Science,2002; 298(5600):1912-1934.
[19]Chambard JC, Renaud L, Pouyssegur J, et al. ERK implication in cell cycle regulation [J]. Biochim Biophys Acta.,2007; 1773(8):1299-1310.
[20]Rajalingam K, Rudel T. Ras-Raf signaling needs prohibitin [J]. Cell Cycle,2005; 4(11):1503-1505.
[21]Robertson JD, Zhivotovsky B. Orrenius S. Review:nuclear events in apoptosis [J]. J Struct Biol,2000; 129(2-3):346-358.
[22]Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer [J]. Oncogene,2007; 26(22): 3291-3310.
[23]McCubrey JA, May S, Duronio V, et al. Serine/threonine phosphorylation in cytokine signal transduction [J]. Lerkemia,2000; 14(1):9-21.
[24]Arbabi S, Maier RV. Mitogen-activated protein kinase [J]. Crit CareMed,2002; 30:874-879.
[25]John M, Kyriakis. The integration of signaling by multiprotein complexes containing Raf kinase [J]. Biochim Biophys Acta,2007; 1773(8):1238-1247.
[26]Yamamoto T, Cui XM, Shuler CF. Role of ERK1/2 signaling during EGF-induced inhibition of palatal fusion [J]. Dev Bio,2003; 260(2):512-521.
[27]Sabio G, Reuver S, Feijoo C, et al. Stress and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38y and ERK1/ERK2 [J]. Biochemical Journal,2004; 380(Pt 1):19-30.
[28]Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1 [J].Adv Pharmacol,2010; 60:1-26.
[29]Min LJ, Mogi M, Iwai M, et al. Signaling mechanisms of angiotensin Ⅱ in regulating vascular senescence [J]. Ageing Res Rev,2009; 8(2):113-121.
[30]Franco M, P e rez-Mend e z O, Martinez F. Interaction of intrarenal adenosine and angiotensin Ⅱ in kidney vascular resistance [J]. Curr Opin Nephrol Hypertens, 2009; 18(1):63-67.
[31]Li J, Li J, Liang F, et al. Electroacupuncture at PC6 (Neiguan) Improves Extracellular Signal-Regulated Kinase Signaling Pathways Through the Regulation of Neuroendocrine Cytokines in Myocardial Hypertrophic Rats [J]. Evid Based Complement Alternat Med. doi:10.1155/2012/792820.
[1]王华主编.《针灸学》.高等教育出版社,2008：184.
[2]石学敏.针灸学[M].北京：中国中医药出版社,2007：195.
[3]严振国.经穴断面解剖图谱[M].上海：上海科学技术出版社,2002：58.
[4]文琛.人的小血管壁神经分布及其与经络气血的关系[J].中国针灸,1981；2：282.
[5]沈雪勇,党瑞山,陈尔瑜,等.胃经腧穴与结缔组织结构和钙元富集关系[J].中国针灸,1998；18(10)：595-596.
[6]张静.针刺厥阴俞、心俞与T4-T5夹脊穴对缺血性心脏病患者心电图即刻效应的对比观察[D].山东中医药大学,2008年.
[7]Lorell BH, Carabello BA. Left ventricular hypertrophy:pathogenesis, detection, and prognosis [J]. Circulation,2000; 102(4):470-479.
[8]Nakagami H, Takemoto M, Liao JK. NADPH oxidase-derived superoxide anion mediates angiotensin Ⅱ-induced cardiac hypertrophy [J]. J Mol Cell Cardio,2003; 35(7):851-859.
[9]Johnson JA. An epsilonPKC-selective inhibitor attenuates back phosphorylation of a low molecular weight protein in cardiac myocytes [J]. Cell Signal,2003; 15(11):123-130.
[10]Russell B, Motlagh D, Ashley WW. Form follows function:how muscle shape is regulated by work [J]. J Appl Physiol,2000; 88(3):1127-1132.
[11]Ozaki M, Kawashima S, Yamashita T, et al. Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion [J]. Circ J,2002; 66(9):851-856.
[12]Toriis, Nakayama K, Yamamoto T, et al. Regulatory mechanisms function of ERK MAP kinases [J]. J Riochem,2004; 136(5):557-561.
[13]Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer [J]. Nat Rev Cancer.2004; 4(12):937-947.
[14]Thorburn J, Frost JA, Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy [J]. J Cell Biol,1994; 126(6):1565-1572.
[15]Bonni A, Brunet A, West A E, et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms [J]. Science,1999; 286(5443):1358-1362.
[16]Haq S, Choukroun G, Lim H, et al. Molkentin JD. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure [J]. Circulation,2001; 103(5):670-677.
[17]Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J]. EMBO J,2000; 19(23):6341-6350.
[18]Wang L, Proud CG Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes [J]. Circ. Res,2002; 91(9):821-829.
[19]Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemia-repeffusion injury by inhibiting events in the early minutes of reperfusian [J]. Cardiovnsc Res.2004; 62(1):74-85.
[20]Sun HY, Wang NP, Kerendi F, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol,2005; 288(4):H1900-1908.
[21]吴刚,杨蕾,刘永锋,等.缺血预处理对大鼠肝脏缺血再灌注损伤保护作用机制的研究[J].中华肝胆外科杂志,2003；9(4)：221-224.
[22]Alvarez-Jaimes L, Feliciano-Rivera M, Centeno-Gonzalez M, et al. Contributions of the mitogen-activated protein kinase and protein kinase C cascades in spatial learning and memory mediated by the nucleus accumbens [J]. J Pharmacol Exp Ther,2005; 314(3):1144-1157.
[23]Lips D J, Bueno O F, Wilkins B J, et al. MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo [J]. Circulation,2004; 109(16): 1938-1941.
[24]Bhatt R R, Jr Ferrell J E. The protein kinase p90 rsk as an essential mediator of cytostatic factor activity [J]. Science,1999; 286(5443):1362-1365.
[25]Baines C P, Zhang J, Wang G W, et al. Mitochondrial PKC epsilon and MAPK form signaling modules in the murine heart:enhanced mitochondrial PKC epsilon-MAPK interactions and differential MAPK activation in PKC epsilon-induced cardioprotection [J]. Circ Res,2002; 90(4):390-397.
[26]Gorin Y, Ricono JM, Wagner B. Angiotensin Ⅱ-induced ERK1/2 activation and protein synthesis are redox-dependent in glomerular mesangial cells [J]. Biochem, 2004; 381(1):231-239.
[27]王智刚,张卫泽,马凌,等.抑制ERK1/2通路激活改善大鼠心房纤维化和缝隙连接蛋白40重构[J].第二军医大学学报,2012；33(3)：259-264.
[28]Merrill WH, Friesinger GC, Graham TP Jr, et al. Long-lasting improvement after septal myectomy for hypertrophic obstructive cardiomyopathy [J]. Ann Thorac Surg,2000; 69(6):1732-1735.
[29]Ritchie RH, Irvine JC, Rosenkranz AC, et al. Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy:NON and beyond [J]. Pharmacol Ther,2009; 124(3):279-300.
[30]Bernardo BC, Weeks KL, Pretorius L, et al. Molecular distinction between physiological and pathological cardiac hypertrophy:Experimental findings and therapeutic strategies [J]. Pharmacol Ther,2010; 128(1):191-227.
[31]Ocaranra M P, Diaz Araya G, Chiong M, et al. Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis [J]. J Cardiovase Pharmacol,2002; 41(2):1246-1254.
[32]Stanton HC, Brenner G, Mayfield ED Jr. Studies on isoproterenol induced cardiomegaly in rats [J]. Am Heart J,1969; 77(1):72-80.
[33]Borges JC, Silva JA Jr, Gomes MA, et al. Tonin in rat heart with experimental hypertrophy [J]. Am J Physiol Heart Circ Physiol,2003; 284(6):2263-2268.
[34]CAM FS, RAY M. Hypertrophic cardiomyopathy:pathological features and molecular pathogenesis [J]. Anadolu Kardiyol Derg,2004; 4(4):327-330.
[1]Ma KW:Acupuncture:Its place in the history of Chinese medicine. Acupunct Med 2000;18:88-99.
[2]Middlekauff HR. Acupuncture in the treatment of heart failure. Cardiol Rev 2004;12(3):171-3.
[3]Schoen AM. Veterinary acupuncture:ancient art to modern medicine. St. Louis, Missouri, U.S.A:Mosby, Inc 2001;19-23:127-48.
[4]Tam KC, Yiu HH. The effect of acupuncture on essential hypertension. Am J Chin Med 1975;3(4):369-75.
[5]Richter A, Herlitz J, Hjalmarson A. Effect of acupuncture in patients with angina pectoris. Eur Heart J 1991; 12(2):175-8.
[6]NIH Consensus Conference. Acupuncture. JAMA 1998;280(17):1518-24.
[7]Ballegaard S, Jensen G, Pedersen F, et al. Acupuncture in severe, stable angina pectoris:a randomized trial. Acta Med Scand 1986;220(4):307-13.
[8]Gao ZW, Yu XZ, Shen AX, et al. Clinical observations on treatment of 220 cases of arrhythmia with acupuncture. Compilation of the abstract of acupuncture and moxibustion papers (Abstract). The First World Conference on Acupuncture-Moxibustion 1987;13-4.
[9]Li P, Tjen-ALooi SC, Longhurst JC. Excitatory projections from arcuate nucleus to ventrolateral periaqueductal gray in electroacupuncture inhibition of cardiovascular reflexes. Am J Physiol Heart Circ Physiol 2006;290(6):2535-42.
[10]Tjen-A-Looi SC, Li P, Longhurst JC. Midbrain vIPAG inhibits rVLM cardiovascular sympathoexcitatory responses during acupuncture. Am J Physiol Heart Circ Physiol 2006;290(6):2543-53.
[11]Tjen-A-Looi SC, Li P, Longhurst JC. Role of medullary GABA, opioids, and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electroacupuncture in cats. Am J Physiol Heart Circ Physiol 2007;293(6):3627-35.
[12]Tsou MT, Ho JY, Lin CH, et al. Proteomic analysis finds different myocardial protective mechanisms for median nerve stimulation by electroacupuncture and by local somatothermal stimulation. Int JMol Med 2004;14(4):553-63.
[13]Li P. Neural mechanisms of the effect of acupuncture on cardiovascular diseases. Satellite Symposium of 34th world congress of the International Union of Physiological Sciences (IUPS), Electroacupuncture:is there a physiological basis? Auckland, New Zealand, pp 5, International Congress Sciences 2002; 1238:71-7.
[14]Li P, Pitsillides KF, Rendig SV, et al. Reversal of reflex-induced myocardial ischemia by median nerve stimulation:a feline model of electroacupuncture. Circulation 1998;97(12):1186-94.
[15]Crisostomo M, Li P, Tjen-A-Looi SC, et al. Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats. JAppl Physiol 2005;98(6):2056-63.
[16]Lin JH, Shih CH, Kaphle K, et al. Acupuncture effects on cardiac functions measured by cardiac magnetic resonance imaging in a feline model. Evid Based Complement Alternat Med 2010;7(2):169-76.
[17]Napadow V, Dhond RP, Purdon P, et al. Correlating acupuncture FMRI in the human brainstem with heart rate variability. Conf Proc IEEE Eng Med Biol Soc 2005;5:4496-9.
[18]Li P, Tjen-A-Looi SC, Guo ZL, et al. Long-loop pathways in cardiovascular electroacupuncture responses. JAppl Physiol 2009;106(2):620-30.
[19]Tjen-A-Looi SC, Li P, Longhurst JC. Processing cardiovascular information in the vlPAG during electroacupuncture in rats:roles of endocannabinoids and GABA. JAppl Physiol 2009; 106(6):1793-9.
[20]Fu LW, Longhurst JC. Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 2009;106(6): 1800-9.
[21]Sakatani K, Kitagawa T, Aoyama N, et al. Effects of acupuncture on autonomic nervous function and prefrontal cortex activity. Adv Exp Med Biol 2010;662: 455-60.
[22]Chang S, Chao WL, Chiang MJ, et al. Effects of acupuncture at Neiguan (PC6) of the pericardial meridian on blood pressure and heart rate variability. Chin J Physiol 2008;51(3):167-77.
[23]Li JS, Yan J, He JF, et al. Effects of electroacupuncture on c-fos expression in nucleus of the solitary tract and electrocardiogram ST (II) in myocardial ischemia rats. Zhen Ci Yan Jiu 2009;34(3):171-4.
[24]Chao DM, Shen LL, Tjen-A-Looi S, et al, Naloxone reverses inhibitory effect of electroacupuncture on sympathetic cardiovascular reflex responses. Am J Physiol 1999;276:2127-34.
[25]Tjen-ALooi SC, Li P, Longhurst JC. Prolonged inhibition of rostral ventral lateral medullary premotor sympathetic neuron by electroacupuncture in cats. Auton Neurosci 2003; 106:119-31.
[26]Zhou W, Fu LW, Guo ZL, et al. Role of glutamate in rostral ventrolateral medulla in acupuncture-related modulation of visceral reflex sympathoexcitation. Am J Physiol Heart Circ Physiol 2007;292(4):1868-75.
[27]Li P, Tjen-A-Looi SC, Guo ZL, et al. An arcuate-ventrolateral periaqueductal gray reciprocal circuit participates in electroacupuncture cardiovascular inhibition. Auton Neurosci 2010;158(1-2):13-23.
[28]Holaday JW. Cardiovascular effects of endogenous opiate systems. Am J Physiol 1983;276:2127-34.
[29]Jin Y, Cao Q, Zhuang D. Function of nucleus of solitary tract in the correlation between heart and acupoint Neiguan. J Trad Chin Med 1988;8:61-8.
[30]Li P, Tjen-A-Looi S, Longhurst JC. Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic responses in cats. Auton Neurosci 2001;89(1-2):38-47.
[31]Moazzami A, Tjen-A-Looi SC, Guo ZL, et al. Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture. JAppl Physiol 2010;108(5):1336-46.
[32]Zhi-Ling Guo, Ali R. Moazzami, Stephanie Tjen-A-Looi, et al. Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture. Brain Res 2008; 1229:125-36.
[33]Coleman MJ, Dampney RA. Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus. Am J Physiol 1995;268:1295-302.
[34]Bago M, Marson L, Dean C. Serotonergic projections to the rostroventrolateral medulla from midbrain and raphe nuclei. Brain Res 2002;945:249-58.
[35]Orer HS, Gebber GL, Barman SM. Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm. Am J Physiol 2008;294:1435-44.
[36]Takayama S, Seki T, Watanabe M, et al. Brief effect of acupuncture on the peripheral arterial system of the upper limb and systemic hemodynamics in humans. JAltern Complement Med 2010;16(7):707-13.
[37]Hunt SP, Lovick TA. The distribution of serotonin, met-enkephalin and beta-lipotropin-like immunoreactivity in neuronal perikarya of the cat brainstem. NeurosciLett 1982;30:139-45.
[38]Arvidsson U, Cullheim S, Ulfhake B, et al. Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem. Synapse 1992;11:85-104.
[39]Krukoff TL. Central actions of nitric oxide in regulation of autonomic functions. Brain Res Rev 1999;30:52-65.
[40]Tjen-A-Looi SC, Phan NT, Longhurst JC. Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin. Am J Physiol Heart Circ Physiol 2001;281(5):2010-7.
[41]Wang J, Chen ZJ, Luo CQ, et al. The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip goldblatt hypertension rat. Acta Physiol Sin 2002;54(2):175-8.
[42]Guo ZL, Longhurst JC. Activation of nitric oxide-producing neurons in the brain stem during cardiac sympathoexcitatory reflexes in the cat. Neuroscience 2003;116(1):167-78.
[43]Wang C, Tian YF, Zhou D, et al. Influence of electroacupuncture on myocardial NO and NOS and intracellular Ca2+ contents in myocardial ischemia-reperfusion injury rats. Zhen Ci Yan Jiu 2010;35(2):113-7.
[44]Zhong H, Li GZ. Study on the mechanism of electroacupuncture of "Neiguan" (PC 6) in inhibiting ventricular arrhythmia induced by hypothalamic electrostimulation in the rabbit. Zhen Ci Yan Jiu 2009;34(11):43-7.
[45]World Health Organization. Guidelines for clinical research in acupuncture. Western Pacific series no.15. Manila, Philippines:WHO Regional Office for the Western Pacific,1995.
[46]Jo HG, Jo GH. Electroencephalogram activity induced by magnetic stimulation on heart meridian. Neurosci Lett 2011.
[47]Zhou Yi Syuu W, Hsiao I, Lin VW, et al. Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation:role of the spinal cord. J Appl Physiol 2006;100(3):926-32.