Electroacupuncture Alleviates Pulmonary and Intestinal Injury in Septic Mice via Inhibiting NLRP3 Inflammasome and Remodeling Gut Microbiota

Abstract

Objective

Electroacupuncture (EA) has emerged as a clinically adopted complementary modality in the management of respiratory and digestive disorders. This investigation sought to elucidate the therapeutic potential of EA against sepsis-induced pulmonary and gastrointestinal injuries, with particular emphasis on delineating its multimodal mechanistical pathways.

Methods

Sepsis was induced in C57BL/6 mice by administeringting lipopolysaccharide (LPS) one hour after EA intervention at the Zusanli (ST36) and Tianshu (ST25) acupoints for eight days. Inflammatory responses and barrier function were evaluated in the lung and colon tissues. Hematoxylin and Eosin (H&E) staining was performed on lung tissues, while colon tissues were subjected to H&E staining, Wheat Germ Agglutinin-Fluorescein Isothiocyanate (WGA-FITC) staining, and Alcian Blue staining. Additionally, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blotting were used to explore potential molecular mechanisms. Furthermore, 16S rRNA gene sequencing was employed to analyze changes in the gut microbiota.

Results

EA ameliorated both pulmonary injury and intestinal damage in septic mice. This protective effect was mediated through significant attenuation of pulmonary and intestinal inflammation, coupled with partial restoration of gut microbiota homeostasis. Specifically, EA inhibited the activation of Nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and mitogen-activated protein kinase (MAPK) pathways, and upregulated the transcription of lung barrier-related factors (MMP2, MMP9, Occludin) in the lung. In addition, EA improved inflammation and reduced damage to the intestinal mucosal barrier in the colon. This was accomplished by decreasing the expression of pro-inflammatory cytokines (IL-1β, TNF-α) and increasing the levels of mucin and glycoproteins. Furthermore, EA intervention altered the structure of the gut microbiota, resulting in a significant increase in the abundance of beneficial bacteria, such as Ruminococcaceae and Roseburia.

Conclusion

EA is a potential adjunct therapy for sepsis-related pulmonary and intestinal injury. The mechanism involves the inhibition of the NLRP3 inflammasome and remodeling of the gut microbiota.

Keywords

Electroacupuncture / Sepsis / Acute lung injury / Intestinal barrier dysfuntion / Gut microbiota / NLRP3 inflammation / MAPK signaling

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Funding

National Natural Science Foundation of China(81473788)

National Key Research and Development Program(2020YFC0845800)

Hubei Provincial Natural Science Foundation and Traditional Chinese Medicine Innovation and Development-of China(2023AFD156)

Educational Commission of Hubei Province of China(D20212003)

Wuhan Knowledge Innovation Project(NO. 2022020801010420)

Hubei Provincial Natural Science Joint Fund(no.2024AFD298)

Wuhan Knowledge Innovation Project(NO. 2023020201020794)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology