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Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats.

ABSTRACT: Adipose-derived stromal cells (ADSCs) have excellent capacities for regeneration and tissue protection, while sevoflurane, as a requisite component of surgical procedures, has shown therapeutic benefit in animal models of sepsis. This study therefore determined if the combination of sevoflurane and ADSCs exerted additional protective effects against acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in rats. The animals were randomized into five groups: (sham operation (group I), CLP followed by mechanical ventilation (group II), CLP plus sevoflurane at 0.5 minimum alveolar concentration (group III), CLP plus intravenous autologous 5?×?106 ADSCs (group IV), and CLP plus sevoflurane and ADSCs (group V). Levels of the pro-inflammatory cytokines tumor necrosis factor-?, transforming growth factor-?1, interleukin-1? and interleukin-6 were significantly increased in CLP rats. Moreover, epithelial sodium channel expression levels and activities of Na/K-ATPase and alveolar fluid clearance were significantly reduced in CLP-induced ALI rats. ADSCs improved all these parameters, and these effects were further enhanced by the addition of sevoflurane. In conclusion, combined treatment with ADSCs and sevoflurane is superior to either ADSCs or sevoflurane therapy alone for preventing ALI. This beneficial effect may be partly due to improved alveolar fluid clearance by the paracrine or systemic production of keratinocyte growth factor and via anti-inflammatory properties.

SUBMITTER: Liang Z

PROVIDER: S-EPMC7426944 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats.

Liang Zuodi Z Zhou Heng H Tang Rurong R Zhang Shuo S Chen Xiaohuan X Pei Ling L

Scientific reports 20200813 1

Adipose-derived stromal cells (ADSCs) have excellent capacities for regeneration and tissue protection, while sevoflurane, as a requisite component of surgical procedures, has shown therapeutic benefit in animal models of sepsis. This study therefore determined if the combination of sevoflurane and ADSCs exerted additional protective effects against acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in rats. The animals were randomized into five groups: (sham operation (group I ...[more]

PMID: 32792558

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Project description:The present study investigated the protective effects of emodin on intestinal epithelial tight junction (TJ) barrier integrity in cecal ligation and puncture (CLP)-induced septic rats and its possible mechanisms of action. Healthy male Sprague-Dawley rats were randomly divided into three groups (n=20 per group): Sham group, CLP group and CLP + emodin group. Animals were sacrificed at 12 and 24 h after the model was established. Abdominal aortic blood and specimens of the ileum were harvested for analysis. The histopathological changes in intestinal mucosa and the ultrastructures of intestinal epithelial cells were investigated using light microscopy and transmission electron microscopy. The integrity of the intestinal barrier was assessed by examining plasma diamine oxidase (DAO) levels and the ratio of urine lactulose to mannitol (L/M). The levels of the intestinal TJ proteins claudin-3, zonula occludens (ZO)-1 and occludin were detected using immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The results showed that the pathological damage to intestinal mucosa and the intestinal tissue injury score in the CLP + emodin group were significantly reduced compared to those of the CLP group, and the differences were more obvious at 24 h compared with 12 h. DAO activity and the L/M ratio in the emodin pre-treatment group decreased significantly at 24 h compared with the CLP groups. The protein and mRNA levels of the TJ proteins claudin-3, ZO-1 and occludin in the emodin pre-treatment groups at 12 and 24 h were increased, while occludin mRNA level was found to be decreased compared with the CLP groups. The present study suggested that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity. Emodin may protect intestinal barrier integrity by elevating expression levels of the TJ proteins claudin-3, ZO-1 and occludin in CLP rats.

Project description:Sepsis is the leading cause of death in intensive care units. MicroRNA-34a (miR-34a) is involved in sepsis progression, while its underlying mechanisms on sepsis-induced lung injury remain obscure. Oxidative stress, pyroptosis, and inhibition of autophagy can result in organ injury. MiR-34a has been reported to regulate oxidative stress and autophagy via inhibiting silent information regulator T1 (SIRT1) and autophagy gene 4B (ATG4B) signaling. This study aimed at identifying the function of miR-34a in oxidative stress, inflammation, pyroptosis, and autophagy in sepsis-induced lung injury. Male 8-week-old C57BL/6 mice were subjected to cecal ligation and puncture and treated with miR-34a antagomir/agomir. Survival (n = 10), histopathological changes (n = 6), and lung wet-to-dry ratio (n = 6) were recorded and assayed. Other detection (n = 6) was performed to investigate the level of oxidative stress, inflammation, pyroptosis, and autophagy in lung tissues. Results showed that miR-34a down-regulation ameliorated lung injury in septic mice as reflected by decreased lung injury scores (decrease from 3.00 ± 0.32 to 2.00 ± 0.32) and wet-to-dry ratio (0.36-fold decrease). MiR-34a down-regulation also decreased reactive oxygen species accumulation (0.36-fold decrease), and promoted superoxide dismutase activity and the expression of SIRT1 (1.24-fold increase), heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down-regulation suppressed inflammatory response and pyroptosis in septic mice, as evidenced by decreased level of pro-inflammatory factors including tumor necrosis factor ?, interleukin-6 (IL-6), IL-1?, and IL-18, activity of caspase-1 (0.51-fold decrease) and expression of nucleotide-binding domain and leucine-rich repeat protein-3 (0.48-fold decrease), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D (0.36-fold decrease), and increased level of anti-inflammatory factors IL-10. MiR-34a down-regulation also enhanced autophagy in septic mice as evidenced by more autolysosomes and elevated expressions of ATG4B (0.90-fold increase), beclin1, ATG9, and LC3 II/I. Among these experiments, miR-34a up-regulation showed opposite effects on oxidative stress, inflammatory response, pyroptosis, and autophagy in septic mice. Additionally, miR-34a could bind to the 3'-untranslated region of SIRT1 and ATG4B. In conclusion, our findings demonstrated that miR-34a was implicated in oxidative stress, inflammation, pyroptosis, and autophagy in the development of sepsis. MiR-34a inhibition had a potential to alleviate sepsis-induced lung injury.

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Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats.

Publications

Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats.

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