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Bone Marrow Mesenchymal Stem Cells Alleviate Acute Severe Pancreatitis and Promote Lung Repair via Inhibiting NLRP3 Inflammasome in Rat

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Abstract

Background

Acute severe pancreatitis (SAP) is a severe acute abdominal disease, which can lead to pancreatic infection and necrosis as well as distant organ damage. Bone marrow mesenchymal stem cells (BMSCs) can exert anti-inflammatory effect on SAP, while NLRP3 inflammasomes play an important role in the inflammatory response. This study aimed to investigate whether BMSCs exert anti-inflammatory effect on SAP by inhibiting NLRP3 inflammasome.

Methods

The rat SAP model was established. Serum amylase, lipase and inflammatory factor levels were measured by ELISA, and the level of tissue injury was assessed by HE staining. The expression of NLRP3 inflammasome was detected by PCR, Western Blot and immunohistochemistry. ML385 was used to block Nrf2 pathway, aiming to investigate whether Nrf2 pathway was involved in the therapeutic effect of BMSCs on SAP by regulating NLRP3 inflammasome expression.

Results

In SAP rats, NLRP3 inflammasome was activated, which became more evident over time. After transplantation of BMSCs, the NLRP3 inflammasome expression decreased at both mRNA and protein levels, the serum levels of amylase, lipase and inflammatory factors decreased, and the pathological scores of the pancreas and lung were both improved. After blocking the Nrf2 pathway, the NLRP3 inflammasome expression increased in the injured pancreas and lung, and the inflammation deteriorated, which inhibited the therapeutic effects of BMSCs on SAP.

Conclusion

The therapeutic effect of BMSC on SAP is at least partially ascribed to the inhibition of NLRP3 inflammasome, and Nrf2 pathway mediates the therapeutic effect of BMSC on SAP by inhibiting NLRP3 inflammasome.

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Data availability

The data that supports the findings of this study are available in the article and in the Supporting Information.

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Acknowledgments

We thank Zhengyu Hu, Wangchen Xie, and Zhilong Ma for their help with this article.

Funding

This work was supported by the Shanghai Fourth People’s Hospital discipline construction project (SY-XKZT-2022-1001) and the Research Project of Science and Technology Commission of Shanghai Municipality (No. 124119a3202).

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Author notes

  1. Jian Gong and Zhaoming Xiong have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 200072, Shanghai, China

    Jian Gong & Zhaoming Xiong

  2. Department of General Surgery, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, 200072, Shanghai, China

    Weidi Yu & Zhenshun Song

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  1. Jian Gong
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  2. Zhaoming Xiong
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Contributions

ZS and ZX: Conceptualization and supervision; JG and WY: Data curation, Writing—original draft, formal analysis, methodology and software.

Corresponding author

Correspondence to Zhenshun Song.

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The authors declare no conflict of interest.

Ethical approval 

All animal experiments are approved by the Animal Ethics Committee of Shanghai Tenth People’s Hospital (SHDSYY-2022-2330).

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Gong, J., Xiong, Z., Yu, W. et al. Bone Marrow Mesenchymal Stem Cells Alleviate Acute Severe Pancreatitis and Promote Lung Repair via Inhibiting NLRP3 Inflammasome in Rat. Dig Dis Sci 69, 135–147 (2024). https://doi.org/10.1007/s10620-023-08189-5

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