Shenfu Injection Mitigates Sepsis-Induced Acute Lung Injury in Rats by Modulating the RIPK3 Signaling Pathway

DOI: https://doi.org/10.62517/jlsa.202507408

Author(s)

Wenhan Xia¹,*, Jian Luo2, Jinghui Fan3, Tingyu Li4

Affiliation(s)

¹Department of Critical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China ²Ji'an County People's Hospital, Ji'an, China 3Yingtan City People's Hospital, Yingtan, China 4Jiangxi University of Chinese Medicine, Nanchang, China *Corresponding Author

Abstract

Objective: This research explored the protective role and underlying mechanism of Shenfu Injection (SFI) in a rat model of sepsis-induced acute lung injury (ALI), with particular attention to the modulation of the receptor-interacting protein kinase 3 (RIPK3) signaling pathway. Methods: A rat model of sepsis-induced acute lung injury (ALI) was generated through the cecal ligation and puncture (CLP) procedure. Animals were randomly assigned to four groups: Sham, CLP, CLP+SFI (10 mL/kg, intraperitoneal), and CLP+SFI high-dose (20 mL/kg). After 24 hours, lung and serum samples were collected. Histopathological alterations in pulmonary tissues were examined using hematoxylin-eosin (H&E) staining and evaluated by lung injury scoring. The wet-to-dry (W/D) ratio was calculated to assess pulmonary edema. Serum concentrations of TNF-α and IL-6 were quantified by ELISA. Expression levels of RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissues were analyzed through Western blotting and immunohistochemistry. Results: Relative to the CLP group, Shenfu Injection (SFI) treatment notably mitigated alveolar structural impairment, suppressed inflammatory cell infiltration, and lowered lung injury scores. SFI administration also markedly reduced the pulmonary wet-to-dry (W/D) ratio and serum concentrations of TNF-α and IL-6. Western blotting revealed that the CLP group exhibited elevated expression of RIPK3 and phosphorylated MLKL, whereas these proteins were significantly diminished in rats receiving SFI. Conclusion: Shenfu Injection (SFI) alleviates sepsis-induced acute lung injury in rats through the suppression of inflammatory responses and the inhibition of RIPK3/MLKL-dependent necroptotic signaling. These results indicate that regulation of the RIPK3 pathway could represent a key mechanism contributing to the protective action of SFI against sepsis-related organ damage.

Keywords

Sepsis; Acute lung injury; Shenfu Injection; RIPK3; Necroptosis; Inflammation

References

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