JLX001 improves myocardial ischemia-reperfusion injury by activating Jak2-Stat3 pathway

• Published in: Life sciences (1973) 2020-09, Vol.257, p.118083-118083, Article 118083
• Main Authors: Yin, Qiyang, Zhao, Bo, Zhu, Jianping, Fei, Yuxiang, Shen, Weiyang, Liang, Bingwen, Zhu, Xiong, Li, Yuman
• Format: Article
• Language: English
• Subjects: Apoptosis; BAX protein; Bcl-2 protein; Cell size; Coronary artery; Creatine; Creatine kinase; Deprivation; DNA nucleotidylexotransferase; Echocardiography; Glucose; H9C2 cells; Heart; IL-1β; In vivo methods and tests; Inflammation; Interleukins; Ischemia; Jak2-Stat3 pathway; Janus kinase 2; JLX001; Kinases; Malondialdehyde; Myocardial ischemia; Myocardial ischemia-reperfusion; Oxidative stress; Oxygen; Pharmacodynamics; Protein expression; Proteins; Reperfusion; Rodents; Staining; Stat3 protein; Superoxide dismutase; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ventricle
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118083

To investigate the preclinical pharmacodynamics and mechanism of JLX001 against myocardial ischemia reperfusion (MI/R) for clinical application. In vivo, SD rats were given intragastric administration for 5 days, and the MI/R model was established by ligating/releasing the left anterior descending coronary artery. In vitro, the oxygen-glucose deprivation/reperfusion (OGD/R) model was established after the drug was pre-incubated for 24 h in H9C2 cells. The infract size was determined by TTC staining. Left ventricular function of MI/R rats was detected by echocardiography. The level of histopathological score was determined by hematoxylin-eosin (HE) staining. The level of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase (CK), lactic dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by relevant kits. The level of apoptosis was measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Hoechst staining. The expression of p-Jak2, p-Stat3, Bax, Bcl-2, TNF-α, IL-1β protein were determined by western blot. JLX001 can significantly improve left ventricular function, reduce myocardial infract size, histopathological score, the level of MDA, CK, LDH, TNF-α, IL-1β and the expression of Bax protein, significantly increase the activity of SOD, Bcl-2 protein expression, p-Jak2 protein expression, p-Stat3 protein expression in rat heart tissues and H9C2 cells. These effects can be reversed by AG490 which is a specific inhibitor of Jak2-Stat3 pathway. JLX001 can alleviate MI/R injury by inhibiting myocardial apoptosis, inflammation, and oxidative stress via Jak2-Stat3 pathway in vivo and in vitro.