Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia

Yan LU; Mei-ling YANG; A-ling SHEN; Shan LIN; Mei-zhong PENG; Tian-yi WANG; Zhu-qing LU; Yi-lian WANG; Jun PENG; Jian-feng CHU

doi:10.1007/s11655-021-2882-z

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Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia

Original Article | Updated：2022-03-29

- Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia
- Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia
- Chinese Journal of Integrative Medicine 2022年28卷第4期页码：319-329
- Affiliations：
  
  1.Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  2.Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  3.Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou (350122),China
  4.Department of Acupuncture and Moxibustion, Third People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
- Author bio：
  
  Dr. CHU Jian-feng, E-mail: jianfengchu@126.com
- Funds：
  
  Natural Science Foundations of Fujian Province(2018J01884);Science and Technology Major Project of Fujian Province(2019YZ014004);Fujian Provincial Health and Family Planning Commission(2018-CX-42);the National Natural Science Foundation of China(81774135)
- DOI：10.1007/s11655-021-2882-z
  中图分类号：
- 纸质出版日期：2022-04，
  
  网络出版日期：2021-12-12，
  
  录用日期：2021-09-05
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Yan LU, Mei-ling YANG, A-ling SHEN, 等. Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2022,28(4):319-329.

Yan LU, Mei-ling YANG, A-ling SHEN, et al. Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2022,28(4):319-329.
Yan LU, Mei-ling YANG, A-ling SHEN, 等. Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2022,28(4):319-329. DOI： 10.1007/s11655-021-2882-z.

Yan LU, Mei-ling YANG, A-ling SHEN, et al. Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia[J]. Chinese Journal of Integrative Medicine, 2022,28(4):319-329. DOI： 10.1007/s11655-021-2882-z.

摘要

目的:

探讨宽胸气雾剂 (KXA) 对异丙肾上腺素 (ISO) 致大鼠心肌损伤模型的影响.

方法:

24只大鼠

按照随机区组设计法随机分为对照组、ISO、KXA低剂量组和高剂量组

连续灌胃10天

第9天和第10天

大鼠被连续2天注射ISO

构建急性心肌缺血模型

以评价KXA对心肌缺血的改善作用. 此外

通过体外血管张力试验检测了KXA对大鼠胸主动脉的舒张作用及其对离子通道的调节作用. 还测试了KXA对钙-钙调蛋白依赖性蛋白激酶Ⅱ (CaMK Ⅱ) /细胞外调节蛋白激酶 (ERK) 信号通路表达的影响.

结果:

KXA显着降低了ISO诱导的大鼠ST段、室间隔厚度、心脏质量指数和心脏组织病理变化的增加. 此外

使用去甲肾上腺素(NE)或氯化钾(KCl)预收缩的胸主动脉环在KXA治疗后以不依赖内皮的方式舒张率增加

并且通过预孵育维拉帕米减弱

与四乙基氯化铵、4-氨基吡啶、格列本脲或氯化钡无关. 在含有K

或NE的无Ca

溶液中

KXA预处理减弱了由CaCl

引起的血管收缩. 此外

KXA预处理抑制了由KCl和NE介导的A7r5细胞中Ca

的积累

显着降低了p-CaMKⅡ和p-ERK水平.

结论:

KXA可能通过抑制钙的流入和释放

激活CaMKⅡ/ERK信号通路

产生血管舒张作用

从而改善心肌损伤.

Abstract

Objective:

To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.

Methods:

Totally 24 rats were radomly divided into control

ISO

KXA low-dose and high-dose groups according to the randomized block design method

and were administered by intragastric administration for 10 consecutive days

and on the 9th and 10th days

rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition

the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by

in vitro

vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ (CaMKⅡ)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.

Results:

KXA significantly reduced the ISO-induced increase in ST-segment

interventricular septal thickness

cardiac mass index and cardiac tissue pathological changes in rats. Moreover

the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner

and was attenuated by preincubation with verapamil

but not with tetraethylammonium chloride

4-aminopyridine

glibenclamide

or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl

in Ca

-free solutions containing K

or NE. In addition

KXA pretreatment inhibited accumulation of Ca

in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMKⅡ and p-ERK levels.

Conclusion:

KXA may inhibit inﬂux and release of calcium and activate the CaMKⅡ/ERK signaling pathway to produce vasodilatory effects

thereby improving myocardial injury.

关键词

Keywords

Kuanxiong Aerosolmyocardial ischemiavasodilationCa2+CaMKⅡ/ERK pathway

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