Time‐Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor‐Induced Myocardial Ischemia Pigs

Abstract

We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF-α and active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF-α and active caspase-3 seemed to be the critical potential target of QSYQ.

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

“…Ameroid constrictors have been used extensively to create animal models of chronic myocardial ischemia, chronic myocardial infarction, and heart failure 5 6 7 9 10 11 12 13 15 16 17 18 19 22 . Although these models can be created through the use of stents, hydraulic occluders, or fixed stenosis occluders, the prevalence of ameroid use in scientific literature allows researchers to more accurately compare the results of their work with previously published studies 5 6 7 9 10 11 12 13 15 16 17 18 19 22 . Another advantage of using the ameroid constrictor is that the procedure is relatively straightforward and can be performed successfully by anyone with reasonable surgical skills, and requires no specialized instruments.…”

“…Once placed around an artery (usually the left anterior descending coronary artery (LAD) or the left circumflex coronary artery (LCX)), the casein material absorbs the surrounding fluid causing the inner lumen to narrow gradually, mimicking the slow stenosis of an artery and resulting finally in full occlusion 9 13 14 . This procedure used by itself or in conjunction with other methods results in a region of chronic myocardial ischemia and/or infarction of the left ventricle of the heart that has been useful for developing and evaluating new imaging techniques 8 10 15 , therapeutic treatments 7 16 17 18 and surgical procedures 19 20 .…”

Simultaneous Determination of Twenty-Five Compounds in Rat Plasma Using Ultra-High Performance Liquid Chromatography-Polarity Switching Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

“…Afterwards, all rats were randomly divided into two groups, namely sham and model groups. The myocardial ischemia model was simulated by left anterior descending (LAD) coronary artery ligation [ 12 ], whilst the rats belonging to the sham group received the similar surgery, however no actual ligation in LAD. All animals were fasted overnight with free access to water prior to oral dosing.…”

“…In our previous studies, rats with myocardial ischemia simulated by left anterior descending coronary artery ligation havebeen proved to be a reliable heart failure model, and a set of investigations have also been carried out concerning the underlying pharmacological mechanisms for the therapeutic benefits of QSKL in pathological rats [ 11 , 12 , 13 , 14 , 15 ]. The primary signal pathways involved in the therapeutic actions have been revealed as well [ 11 , 12 , 13 , 14 , 15 ], however, the components responsible for the therapeutic outcomes remain unclear. Therefore, an attempt to reveal the effective components, the current study through a multi-component pharmacokinetic study of QSKL in both sham and model rats was carried out.…”

中药复方多成分多靶点协同增效药理药效评价体系

“…在药理机制研究方面, 针对重大复杂疾病冠心 病, 采用疾病潜在靶标群与药物成分群, 综合考虑 ADMET, 利用 drugcipher 的方法进行成分-靶标之间 的预测, 成功地完成了 1 个新药-芪参颗粒的全部临床 前研究. 实验证实, 该复方不仅能够在一定程度上提 高心功能指数 [31] , 而且有效地逆转心室肥厚功能, 该 机 制 与 调 控 肾 素 -血 管 紧 张 素 -醛 固 酮 系 统 (reninangiotensin-aldosterone system, RAAS)不同功能的血管 紧张素Ⅱ受体(receptors of angiotensin Ⅱ, ATs)和血管 紧张素转化酶(angiotensin converting enzymes, ACEs) 密 切 相 关 [32] , 尤 其 表 现 出 血 管 紧 张 素 Ⅱ 1 型 受 体 (angiotensin Ⅱ type 1 receptor, AT1)阻断和血管紧张 素转化酶 2(angiotensin converting enzymes 2, ACE2)激 活的双向调节作用 [33] . 还原型烟酰胺腺嘌呤二核苷酸 磷 酸 氧 化 酶 (nicotinamide adenine dinucleotide phosphate-oxidases, NOXs)和信号传导与转录激活因 子 3(signal transducer and activator of transcription 3, STAT3)通路也被同时抑制 [34] , 尤其对 NOX4 和环氧酶 (cyclooxygenases, COXs)介导的心室重塑效果显著 [35] .…”