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Research Paper|Volume 15, Issue 16|pp 8501—8517

Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4/NF-κB/IKKα and JAK2/STAT3 signaling pathways

Xiang-Fei Kang1, Xiao-Li Lu4, Cheng-Fei Bi1,3, Xiao-Dong Hu1, Ying Li1, Jin-Kui Li1, Li-Shan Yang1, Jia Liu2, Lei Ma1, Jun-Fei Zhang1,3
  • 1Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
  • 2Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
  • 3School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, Ningxia, China
  • 4Laboratory Animal Centre, Ningxia Medical University, Yinchuan 750000, Ningxia, China
* Equal contribution
Received: May 23, 2023Accepted: July 20, 2023Published: August 30, 2023
https://doi.org/10.18632/aging.204990

Copyright: © 2023 Kang 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: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms.

Methods: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue.

Results: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1β, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05).

Conclusions: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.