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α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB Pathway

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Abstract

Chronic diabetes mellitus compromises the vascular system, which causes organ injury, including in the lung. Due to the strong compensatory ability of the lung, patients always exhibit subclinical symptoms. Once sepsis occurs, the degree of lung injury is more severe under hyperglycemic conditions. The α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating inflammation and metabolism and can improve endothelial progenitor cell (EPC) functions. In the present study, lung injury caused by sepsis was compared between diabetic rats and normal rats. We also examined whether α7nAChR activation combined with EPC transplantation could ameliorate lung injury in diabetic sepsis rats. A type 2 diabetic model was induced in rats via a high-fat diet and streptozotocin. Then, a rat model of septic lung injury was established by intraperitoneal injection combined with endotracheal instillation of LPS. The oxygenation indices, wet-to-dry ratios, and histopathological scores of the lungs were tested after PNU282987 treatment and EPC transplantation. IL-6, IL-8, TNF-α, and IL-10 levels were measured. Caspase-3, Bax, Bcl-2, and phosphorylated NF-κB (p-NF-κB) levels were determined by blotting. Sepsis causes obvious lung injury, which is exacerbated by diabetic conditions. α7nAChR activation and endothelial progenitor cell transplantation reduced lung injury in diabetic sepsis rats, alleviating inflammation and decreasing apoptosis. This treatment was more effective when PNU282987 and endothelial progenitor cells were administered together. p-NF-κB levels decreased following treatment with PNU282987 and EPCs. In conclusion, α7nAChR activation combined with EPC transplantation can alleviate lung injury in diabetic sepsis rats through the NF-κB signaling pathway.

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DATA AVAILABILITY

All data generated or analysed during this study are available from the corresponding author on reasonable request.

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Funding

This study was supported by a grant from the Natural Science Foundation of Heilongjiang Province (grant no. LH2021H026).

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  1. Xiaoyun Zhang, Haixu Wang, and Xuemin Cai contributed equally as first co-authors.

Authors and Affiliations

  1. Department of Anesthesiology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, Heilongjiang, China

    Xiaoyun Zhang, Enran Liu, Zhiyuan Li, Tao Jiang, Dongmei Li & Wengang Ding

  2. Department of Anesthesiology, the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China

    Haixu Wang

  3. Department of Anesthesiology, Nanchong Central Hospital, Nanchong, Sichuan, China

    Xuemin Cai

  4. Department of Anesthesiology, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China

    Aijia Zhang

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Contributions

Conception and design of the study: Wengang Ding, Xiaoyun Zhang, Haixu Wang, Xuemin Cai. Acquisition of the data: Xiaoyun Zhang, Haixu Wang and Xuemin Cai. Analysis and/or interpretation of the data: Wengang Ding, Xiaoyun Zhang, Haixu Wang, Xuemin Cai, Enran Liu, Zhiyuan Li, Tao Jiang. Drafting the manuscript: Xiaoyun Zhang. Revising the manuscript critically for important intellectual content: Wengang Ding, Xiaoyun Zhang, Haixu Wang, Xuemin Cai, Enran Liu, Zhiyuan Li, Tao Jiang, Dongmei Li. Approval of the version of the manuscript to be published: Wengang Ding, Xiaoyun Zhang, Haixu Wang, Xuemin Cai, Enran Liu, Zhiyuan Li, Tao Jiang, Dongmei Li. All the authors read and approved the final manuscript.

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Correspondence to Wengang Ding.

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All animal protocols were approved by the Animal Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (approval no. SYDW2021-009).

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Zhang, X., Wang, H., Cai, X. et al. α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB Pathway. Inflammation (2024). https://doi.org/10.1007/s10753-024-01980-0

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