Li Yu Hong, Yu Bin, Duan Zhen Zhen, Akinyi Olunga Mary, Yu Jia Hui, Zhou Kun, Zhang Yue, Gao Xiu Mei
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China; Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China; Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China; Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China; Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, P. R. China.
PLoS One. 2014 Mar 24;9(3):e92415. doi: 10.1371/journal.pone.0092415. eCollection 2014.
Shen Fu Injection (SF), which consisted of Red ginseng extraction injection (RG) and prepared aconite extraction injection (RA), is a traditional Chinese medicine mainly used for various cardiac diseases. This study is to analyse SF's effects on cardiac performance and coronary circulation. And the coronary dilating effect and mechanism of the above three injections were also explored.
Mature male guinea pigs were used as our animal model. We employed two types of perfusion methods (constant pressure and constant flow) in vitro, using Langendorff heart preparations to observe the cardiac function and coronary response to SF (1/200). The coronary dilation effects of the above three injections (1/800, 1/400 and 1/200) were recorded at basal coronary resting tone and when coronary vessels were pre-contracted with a thromboxane A2 analogue (U46619), in the presence or the absence of the inhibitor of nitric oxide synthesis (L-NAME, 10-4 M), the blocker of Ca2+-activated potassium channel(TEA, 10-3 M), or the blocker of adenosine triphosphate (ATP)-sensitive potassium channel (glybenclamide) (10-5 M).
When perfused with constant pressure, SF significantly increased coronary flow, left ventricular developed pressure (LVDP) and the rate-pressure product (RPP). When perfused with constant flow, SF produced a significant reduction in the coronary perfusion pressure (CPP), LVDP and RPP. The coronary vasodilatation response of the above three injections can be reduced by L-NAME but was unaffected by TEA or glybenclamide when coronary vessels were pre-contracted with U46619 but not at resting tone. SF, RG and RA can all up-regulate eNOS expression in the human umbilical vein cells (EA.hy926).
We demonstrated that SF does not contribute to the inotropic change of myocardium whose improvement is due to alternation of coronary flow. The coronary dilation effect of SF was mediated through RG and RA, via promoting NO release.
参附注射液（SF）由红参提取物注射液（RG）和制附子提取物注射液（RA）组成，是一种主要用于治疗各种心脏疾病的中药。本研究旨在分析参附注射液对心脏功能和冠脉循环的影响。同时，还探讨了上述三种注射液的冠脉扩张作用及其机制。
选用成年雄性豚鼠作为动物模型。采用两种体外灌注方法（恒压和恒流），利用Langendorff心脏标本观察参附注射液（1/200）对心脏功能和冠脉的反应。记录上述三种注射液（1/800、1/400和1/200）在基础冠脉静息张力下以及冠脉血管用血栓素A2类似物（U46619）预收缩时，在存在或不存在一氧化氮合成抑制剂（L-NAME，10-4 M）、钙激活钾通道阻滞剂（TEA，10-3 M）或三磷酸腺苷（ATP）敏感性钾通道阻滞剂（格列本脲）（10-5 M）的情况下的冠脉扩张作用。
恒压灌注时，参附注射液显著增加冠脉流量、左心室舒张末压（LVDP）和速率压力乘积（RPP）。恒流灌注时，参附注射液使冠脉灌注压（CPP）、LVDP和RPP显著降低。当冠脉血管用U46619预收缩但在静息张力下时，上述三种注射液的冠脉血管舒张反应可被L-NAME减弱，但不受TEA或格列本脲影响。参附注射液、红参提取物注射液和制附子提取物注射液均可上调人脐静脉细胞（EA.hy926）中内皮型一氧化氮合酶（eNOS）的表达。
我们证明参附注射液对心肌的变力作用无贡献，其改善是由于冠脉血流的改变。参附注射液的冠脉扩张作用是通过红参提取物注射液和制附子提取物注射液介导的，通过促进一氧化氮释放实现。
