Research Paper Volume 15, Issue 10 pp 4374—4390
Xuebijing injection protects against sepsis-induced myocardial injury by regulating apoptosis and autophagy via mediation of PI3K/AKT/mTOR signaling pathway in rats
- 1 Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
- 2 Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
- 3 School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, Ningxia, China
Received: February 6, 2023 Accepted: May 9, 2023 Published: May 22, 2023
https://doi.org/10.18632/aging.204740How to Cite
Copyright: © 2023 Bi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Apoptosis and autophagy are significant factors of sepsis induced myocardial injury (SIMI). XBJ improves SIMI by PI3K/AKT/mTOR pathway. Present study is devised to explore the protective mechanism of XBJ in continuous treatment of SIMI caused by CLP.
Methods: Rat survival was first recorded within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and XBJ group. The animals in each group were divided into 12 h group, 1 d, 2 d, 3 d and 5 d according to the administration time of 12 hours, 1 day, 2 days, 3 days or 5 days, respectively. Echocardiography, myocardial injury markers and H&E staining were used to detect cardiac function and injury. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis was assayed by TUNEL staining. Apoptosis and autophagy related proteins regulated by the PI3K/AKT/mTOR signaling pathway were tested using western blot.
Results: XBJ increased the survival rate in CLP-induced septic Rat. First of all, the results of echocardiography, H&E staining and myocardial injury markers (cTnI, CK, and LDH levels) showed that XBJ could effectively improve the myocardial injury caused by CLP with the increase of treatment time. Moreover, XBJ significantly decreased the levels of serum inflammatory cytokines IL-1β, IL-6 and TNF-α in SIMI rats. Meanwhile, XBJ downregulated the expression of apoptosis-related proteins Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cytochrome C and Cleaved-PARP, while upregulated the protein levels of Bcl-2 in SIMI rats. And, XBJ upregulated the expression of autophagy related protein Beclin-1 and LC3-II/LC3-I ratio in SIMI rats, whereas downregulated the expression of P62. Finally, XBJ administration downregulated the phosphorylation levels of proteins PI3K, AKT and mTOR in SIMI rats.
Conclusions: Our results showed that XBJ has a good protective effect on SIMI after continuous treatment, and it was speculated that it might be through inhibiting apoptosis and promoting autophagy via, at least partially, activating PI3K/AKT/mTOR pathway in the early stage of sepsis, as well as promoting apoptosis and inhibiting autophagy via suppressing PI3K/AKT/mTOR pathway in the late stage of sepsis.
Abbreviations
XBJ: Xue Bi Jing Injection; SIMI: sepsis-induced myocardial injury; CLP: cecal-ligation and puncture; TUNEL: TdT mediated dUTP biotin nick-end labeling; CTnI: cardiac troponin I; CK: creatine kinase; LDH: lactate dehydrogenase; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; HE: Hematoxylin and Eosin; ELISA: Enzyme-linked Immunosorbent Assay; IL-1β: interleukin-1β; TNF-α: tumor necrosis factor-α.