Protective effect of Ulinastatin on acute lung injury in diabetic sepsis rats

Jin, Zhe; Li, Mengyun; Tang, Li‐Juan; Zhang, Yufeng; Chen, Kai

doi:10.1016/j.intimp.2022.108908

Cited by 13 publications

(7 citation statements)

References 29 publications

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“…Although the mechanisms underlying POCD have not been elucidated, numerous studies have demonstrated that POCD is associated with neuroinflammation [ 12 , 13 ]. The blood–brain barrier (BBB) plays a critical role in brain homeostasis.…”

Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

Cho,

In,

Lee

et al. 2024

IJMS

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This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

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Section: Discussionmentioning

confidence: 99%

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

Cho,

In,

Lee

et al. 2024

IJMS

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“…The lung is the target organ of diabetes and sepsis. Lung injury worsens when sepsis occurs under diabetic conditions [33]. CAP and stem cell treatment have been con rmed to protect the lung from injury [15,16,34].…”

Section: Discussionmentioning

confidence: 99%

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

Zhang,

Wang,

Cai

et al. 2024

Inflammation

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Chronic diabetes mellitus compromises the vascular system, which causes organ injury, including in the lung. Due to the strong compensatory ability of the lung, it always shows subclinical symptoms. Once sepsis occurs, the degree of lung injury is more severe under hyperglycemia. α7 nicotinic acetylcholine receptors (α7nAChRs) play an important role in regulating in ammation and metabolism, which could improve endothelial progenitor cell functions. In this study, we examined the role of diabetes mellitus during sepsis and whether α7nAChR activation combined with endothelial progenitor cell transplantation can protect the lung from septic and diabetic impairments. Type 2 diabetic model rats were induced by a high-fat diet and streptozotocin. Then, these rats were exposed to lipopolysaccharide in a two-hit manner to cause sepsis. The oxygenation index, wet-to-dry ratio and histopathological score 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, NF-κB levels were blotted. Sepsis caused obvious lung injury, which was exacerbated by diabetic conditions. α7nAChR activation and endothelial progenitor cell injection reduced injury in diabetic rats with sepsis, alleviating in ammation and decreasing apoptosis. This treatment was more effective when PNU282987 and endothelial progenitor cells were administered together. The phosphorylation of NF-κB was inhibited during this process. Activating α7nAChRs and endothelial progenitor cell transplantation alleviated the lung injury in diabetic rats with sepsis. During this process, the phosphorylation of NF-κB was reduced.

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“…Due to the strong compensatory ability of the lung, symptoms of dysfunction were not signi cant. However, when sepsis occurs, in ammatory attack damages the diabetic lung, and there is apparent pulmonary dysfunction [33].…”

Section: Discussionmentioning

confidence: 99%

α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB and JAK2/STAT3 Pathways

Zhang

Wang

Cai

et al. 2023

Preprint

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Background: Chronic diabetes mellitus compromises the vascular system, which causes organ injury, including in the lung. Due to the strong compensatory ability of the lung, it always shows subclinical symptoms. Once sepsis occurs, the degree of lung injury is more severe under hyperglycaemia. α7nAChRs play an important role in regulating inflammation and metabolism. Our previous study demonstrated that PNU282987, an α7nAChR agonist, could improve endothelial progenitor cell functions. In this study, we examined the role of diabetes mellitus during sepsis and whether α7nAChR activation combined with endothelial progenitor cell transplantation can protect the lung from septic and diabetic impairments. Methods: Type 2 diabetic model rats were induced by a high-fat diet and streptozotocin. Then, these rats were exposed to lipopolysaccharide in a two-hit manner to cause sepsis. The oxygenation index, wet-to-dry ratio and histopathological score of the lungs were tested after PNU282987 treatment and EPC transplantation. IL-6, IL-8, TNF-α and IL-10 levels were measured by ELISA. Caspase-3, Bax, Bcl-2, NF-κB, phosphorylated JAK2 and phosphorylated STAT3 levels were measured by western blotting to investigate apoptosis and the underlying mechanism. Results:Sepsis caused obvious lung injury, which was exacerbated by diabetic conditions. α7nAChR activation and endothelial progenitor cell injection reduced injury in diabetic rats with sepsis, alleviating inflammation and decreasing apoptosis. This treatment was more effective when PNU282987 and endothelial progenitor cells were administered together. The JAK2/STAT3 signalling pathway was activated during this process, and the phosphorylation of NF-κB was inhibited. Conclusion: Activating α7nAChRs and endothelial progenitor cell transplantation alleviated the lung injury in diabetic rats with sepsis. Combining PNU282987 with endothelial progenitor cell transplantation showed better results than either treatment alone. During this process, the JAK2/STAT3 signalling pathway was activated, and NF-κB was inhibited.

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Protective effect of Ulinastatin on acute lung injury in diabetic sepsis rats

Cited by 13 publications

References 29 publications

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

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

α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB and JAK2/STAT3 Pathways

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