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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Stellate Ganglion Block Attenuates LPS-Induced Acute Lung Injury by Activating Sirt3 Regulation of Oxidative Stress
Shiyun Dai1,2, Jun Ji3, Rongrong Li1
1Department of Anesthesiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Abstract:
Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1β, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1β and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.
Insights
Stellate ganglion blocks (SGB) can reduce lung injury by activating Sirt3 signaling. This process helps regulate oxidative stress and inflammation, offering a new protective strategy for acute lung injury (ALI).
Area of Science:
- Pulmonary Medicine
- Immunology
- Cellular Signaling
Background:
- Stellate ganglion blocks (SGBs) are used for pain but their role in acute lung injury (ALI) is unclear.
- Previous studies suggest SGBs may attenuate ALI in animal models, necessitating further mechanistic investigation.
Purpose of the Study:
- To elucidate the molecular mechanisms by which SGBs attenuate lipopolysaccharide (LPS)-induced ALI in rats.
- To investigate the role of Sirt3 signaling in mediating the protective effects of SGBs against ALI.
Main Methods:
- Rats were divided into control, saline, LPS, and LPS + SGB groups.
- Evaluated lung tissue damage, blood gases, macrophage differentiation, inflammatory cytokines (IL-1β, IL-6, IL-10), oxidative stress markers (ROS, CYP-D, T-SOD, Mn-SOD, CAT), and Sirt3 signaling pathway proteins (JAK2/STAT3, NF-κb p65, CIRP, NLRP3).
Main Results:
- SGB treatment attenuated lung damage, improved oxygenation, and promoted M2 macrophage differentiation.
- SGB reduced pro-inflammatory cytokines (IL-1β, IL-6) and increased anti-inflammatory IL-10.
- SGB inhibited oxidative stress (ROS, CYP-D) and enhanced antioxidant enzyme activity (T-SOD, Mn-SOD, CAT).
- SGB upregulated Sirt3 and downregulated JAK2/STAT3, NF-κb p65, CIRP, and NLRP3 signaling.
Conclusions:
- SGB attenuates LPS-induced ALI by activating Sirt3-mediated regulation of oxidative stress and inflammation.
- SGB represents a potential prophylactic strategy for LPS-induced ALI.
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