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Dysregulated B7H4/JAK2/STAT3 Pathway Involves in Hypertriglyceridemia Acute Pancreatitis and Is Attenuated by Baicalin

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Abstract

Background

Patients with hypertriglyceridemia (HTG) are prone to develop more severe acute pancreatitis (AP). However, the specific molecular mechanism still has not been elaborated clearly, and effective drugs for treating HTG-AP are not yet readily available. Baicalin is an ingredient isolated from a natural product that with potential to attenuate inflammation and pain in AP.

Aims

The aim of the present study was to explore the effect of baicalin on HTG-AP and the possible mechanism involved.

Methods

A mouse model of HTG-AP was successfully established by administering Poloxamer 407 and l-arginine intraperitoneally. We analyzed pathological changes, and performed TUNEL staining, DHE staining, and western blot to detect apoptosis, inflammation, oxidative stress, and B7H4/JAK2/STAT3 signaling in the pancreas.

Results

Treatment with baicalin decreased serum triglyceride, cholesterol, lipase, amylase levels, and attenuated pancreatic edema. After intervention with baicalin, apoptosis and inflammation in HTG-AP mice were alleviated, as indicated by the decrease of Bax, cleaved-caspase-3, IL-6, TNF-α, and IL-1β. Baicalin also alleviated oxidative stress by decreasing NOX2, increasing SOD2 protein expression, and regulating Nrf2/Keap1 signaling in HTG-AP mice. Furthermore, baicalin decreased the upregulated B7H4/JAK2/STAT3 pathway in HTG-AP.

Conclusions

In conclusion, our data suggested that baicalin could attenuate HTG-AP, possibly through regulating B7H4/JAK2/STAT3 signaling.

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Funding

This work was supported by National Natural Science Foundation of China (No. 81900740), Scientific Research Funding of Tianjin Medical University Chu Hsien-I Memorial Hospital (No. ZXY-YJJ2021-4), and Tianjin Health Commission Science and Technology Project (No. QN20025).

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Author notes

  1. Jie Yang, Fei Han, and Guanghai Wu have contributed equally to this study.

Authors and Affiliations

  1. NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China

    Jie Yang, Fei Han, Ya Dong, Hang Su & Jun Li

  2. Department of General Surgery, Tianjin Union Medical Center, Tianjin, 300121, China

    Guanghai Wu & Jing Xu

Authors
  1. Jie Yang
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  2. Fei Han
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  3. Guanghai Wu
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  4. Ya Dong
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  5. Hang Su
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  6. Jing Xu
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  7. Jun Li
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Contributions

JX and JL contributed to research design and critical revision of the manuscript. JY and FH contributed to the design of study, conduction of the experiment and the manuscript draft. GW contributed to research design, discussion of results, and performed data analysis. YD and HS were responsible in the assistance of the completion of the experiments.

Corresponding author

Correspondence to Jun Li.

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Conflict of interest

The authors declare that there is no conflict of interests.

Ethical approval

The ethics governing the use and conduct of experiments on animals were strictly observed, and the experimental protocol was approved by the Experimental Animal Ethical Committee of Tianjin Medical University (Approval NO. DXBYY-IACUC-2022044).

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Yang, J., Han, F., Wu, G. et al. Dysregulated B7H4/JAK2/STAT3 Pathway Involves in Hypertriglyceridemia Acute Pancreatitis and Is Attenuated by Baicalin. Dig Dis Sci 68, 478–486 (2023). https://doi.org/10.1007/s10620-022-07606-5

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  • DOI: https://doi.org/10.1007/s10620-022-07606-5

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