Alleviation of isoproterenol-induced myocardial fibrosis in mice by autophagy regulated by Astragaloside Ⅳ through activating ROCK/JNK pathway
10.12206/j.issn.2097-2024.202212056
- VernacularTitle:黄芪甲苷激活ROCK/JNK介导自噬减轻异丙肾上腺素诱导的小鼠心肌纤维化
- Author:
Feifei WU
1
;
Xiaoqi ZHANG
1
;
Jing LIAN
1
;
Jing YANG
1
;
Mengen ZHAI
1
;
Rui QIAO
2
;
Chennian XU
3
,
4
;
Tingting YANG
1
Author Information
1. Department of Cardiovascular Surgery, the First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China.
2. Department of the First Cadre Ward, General Hospital of Northern Theater Command, Shenyang 110016, China.
3. Department of Cardiovascular Surgery, the First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
4. Department of Cardiothoracic Surgery, the Hospital of 79th Group Army, Liaoyang 111000, China.
- Keywords:
myocardial fibrosis;
autophagy;
ROCK/JNK;
astragaloside Ⅳ;
mice
- From:
Journal of Pharmaceutical Practice
2023;41(8):478-484
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of astragaloside Ⅳ(AS-Ⅳ) activating ROCK/JNK to regulate autophagy in improving isoproterenol (ISO) induced myocardial fibrosis (MF) in mice. Methods The mice were randomly divided into control operation group (Control group), ISO induced myocardial fibrosis group (MF group), AS-Ⅳ treatment group (AS-Ⅳ group) and combination group of astragaloside IV and Y-33075 (ROCK inhibitor) (astragaloside IV+Y-33075 group). After repeated administration for 30 days. The serum levels of LDH, BNP, CTGF in each group were detected. The cardiac function was detected by ultrasound. Myocardial structure and tissue fibrosis degree in each group were detected by Sirius Red and Masson staining. Oxidative stress (ROS) levels in myocardial tissue of each group were detected by DHE staining and the expression of ROCK, JNK, Atg5, Beclin 1, and LC3 Ⅰ/Ⅱ in myocardial tissue were detected by Western blotting. Results Compared with AS-Ⅳ group, the EF value of AS-Ⅳ+Y-33075 group decreased and the degree of myocardial fibrosis increased (P<0.05). The serum level of LDH, BNP, CTGF increased and the level of ROS in myocardial tissue increased while the expression of ROCK, JNK, Atg5, Beclin 1, LC3 Ⅰ/Ⅱ decreased (P<0.05). Y-33075 could block the protective effect of AS-Ⅳ on myocardial injury induced by MF and inhibit the regulation of AS-Ⅳ on ROCK and JNK. Conclusion AS-Ⅳ could attenuate myocardial fibrosis in mice by activating ROCK/JNK signal and promoting autophagy.
