Mechanisms of Fufang Danshen tablets on treating heart failure via regulating AT₁-mediated PLA2-COX2/5-LOX metabolic pathway.
10.19540/j.cnki.cjcmm.2018.0083
- Author:
Yi ZHANG
1
;
Yong WANG
2
;
Hui MENG
1
;
Wen-Ji LU
3
;
Qi-Xin WANG
1
;
Qian ZHANG
2
;
Chun LI
1
;
Peng-Fei TU
1
Author Information
1. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
2. School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
3. College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
- Publication Type:Journal Article
- Keywords:
Fufang Danshen tablets;
arachidonic acid metabolism;
heart failure;
myocardial fibrosis
- From:
China Journal of Chinese Materia Medica
2018;43(12):2593-2599
- CountryChina
- Language:Chinese
-
Abstract:
Myocardial fibrosis (MF) is an important pathological change involved in the progress from myocardial infarction (MI) to heart failure(HF). Metabolic disorder of arachidonic acid (AA) in cardiomyocytes plays an important role in process of MF. Fufang Danshen tablets is a traditional Chinese medicine (TCM), which showed significant effect on coronary heart diseases and anti-MF. However, the underlying mechanism of anti-MF remains unclear. In this study, HF animal model of myocardial infarction was established by ligation of left anterior descending coronary artery. The heart function of rats in each group was evaluated by echocardiography and hemodynamic measurement. Histological examination, TUNEL and Western blot were used to detect the levels of MF and proteins related to AA metabolism. As a result, MI significantly decreased the levels of ejection fraction (EF), ejection fraction (FS) and left ventricular systolic pressure (LVSP), and these decreases were significantly improved by the treatment of Fufang Danshen tablets. Besides, Fufang Danshen tablets treatment down-regulated the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum. HE, Masson and TUNEL staining results showed that Fufang Danshen tablets treatment could inhibit the inflammatory cells infiltration and attenuate the fibrosis and apoptosis to exert cardioprotective effect. Western blot indicated that Fufang Danshen tablets treatment down-regulated the expressions of AT₁, MMP2, MM9, while up-regulated the expression of AT₂ to inhibit MF. Further mechanism study indicated that Fufang Danshen tablets inhibited MF by down-regulated the expressions of AA metabolism, such as PLA2, P450, COX2 and 5-LOX. In summary, Fufang Danshen tablets can effectively inhibit MF in the ischemic area after MI in rats. The mechanism is related to the regulation of AT₁-mediated PLA2-COX2 metabolic pathway.
