A comparative study of changes of autophagy in rat models of CLP versus LPS induced sepsis

Zhang, Binglun; Liu, Chunfeng; Yang, Ni; Wang, Xiangdie

doi:10.3892/etm.2017.4758

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…24 A previous study revealed significant increases in autophagic activity at 12 and 24 h following CLP. 25 Although transient autophagy may have a protective effect, continuous activation of autophagy causes apoptosis in an inflammatory microenvironment. 26 The current study also found that inhibition of Hsp70 promoted autophagy, consistent with previous results.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy

Wang¹,

Zhu²,

Zhou

et al. 2020

Hum Exp Toxicol

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Objectives: Increasing evidence suggests that heat shock protein 70 (Hsp70) has a protective effect in sepsis-induced cardiomyopathy; however, the protective mechanism remains unclear. Methods: Previous studies have also implicated autophagy in sepsis-induced cardiomyopathy. The aim of the current study was to reveal the protective mechanisms of Hsp70 in sepsis-induced cardiomyopathy using a cecal ligation and puncture (CLP) rat sepsis model. The roles of Hsp70 and autophagy in sepsis-induced cardiomyopathy were investigated by pretreating rats with the Hsp70 inhibitor quercetin or the autophagy inhibitor 3-methyladenine (3-Ma) before CLP. We also investigated the protective mechanisms of Hsp70 and the relationship between Hsp70 and autophagy in vitro by stimulating H9c2 cells with lipopolysaccharide (LPS) to simulate sepsis. Results: The result show that inhibition of Hsp70 promoted sepsis-induced death in rats, while inhibition of autophagy inhibited sepsis-induced death. These results suggested that both Hsp70 and autophagy were involved in sepsis-induced cardiomyopathy. Overexpression of Hsp70 in H9c2 myocardial cells in vitro suppressed LPS-induced apoptosis, while inhibition of autophagy with 3-Ma also decreased LPS-induced H9c2 cell apoptosis, suggesting that the protective effect of Hsp70 in sepsis-induced cardiomyopathy was related to autophagy regulation. Conclusion: Overall, these results suggested that Hsp70 protected against sepsis-induced cardiac impairment by attenuating sepsis-induced autophagy.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy

Wang¹,

Zhu²,

Zhou

et al. 2020

Hum Exp Toxicol

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“…Emodin may also maintain the integrity of the intestinal epithelial TJ barrier by promoting the expression of TJ proteins, including claudin-3, ZO-1 and occludin. CLP-induced sepsis is the most commonly used animal modelling method for sepsis (28). This model accurately represents the progression and properties of human sepsis.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of emodin on intestinal epithelial tight junction barrier integrity in rats with sepsis induced by cecal ligation and puncture

Guo

Zhang

et al. 2020

Exp Ther Med

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Αbstract. 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.

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“…Intraperitoneal injection of LPS, though, is a simpler and easier approach. This makes the LPS model better than the CLP model concerning the perturbation of the underlying molecular biological mechanisms in the brain of the model animals [27]. Therefore, we have used exactly the LPS intraperitoneal injection to establish a sepsis model in mice in our research.…”

Section: Discussionmentioning

confidence: 99%

IL-1β regulates TRPM2 channel in astrocytes and aggravates their apoptosis during lipopolysaccharide induced cognitive impairment in mice

Yang

Jia

Wang

et al. 2022

Preprint

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Background: Cognitive dysfunction after sepsis is the most serious complication after discharge of sepsis patients, and its pathogenesis is related to the inflammation of the central nervous system caused by the damaged blood-brain barrier. Interleukin-1β (IL-1β) is a key factor in sepsis-induced cognitive dysfunction in mice. Several investigations have suggested that TRPM2 (transient receptor potential melastatin-2) performs a vital task in immune response and inflammation. The aim of this exploration was to discover the importance of IL-1β in apoptosis in the hippocampal astrocytes of septic mice through in vitro and in vivo assessments. Methods: mouse severe inflammatory was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 5 mg kg–1), The Morris water maze task and fear conditioning test were used to investigate cognitive functions on the 7th day after LPS injection. Western blotting was implemented to detect the levels of IL-1β , TRPM2 and GFAP. Flow cytometry was employed to ascertain the effects of IL-1β and TRPM2-siRNA on the apoptosis of astrocytes. Immunofluorescent staining was used to examine the expression levels of GFAP and TRPM2 in hippocampus of mice .Results: Intraperitoneal injection of LPS caused cognitive dysfunction in mice, which can be reversed by down-regulation of IL-1β expression in the hippocampus. Elevated expression of IL-1β and TRPM2 were observed in hippocampus from the mouse after LPS injection. Specifc knockdown of IL-1β mRNA expression rescued the elevated expression of TRPM2. Accordingly, specifc knockdown of TRPM2 expression improved the cognitive impairment induced by Intraperitoneal injection of LPS.Conclusions: Elevated expression of IL-1β in the hippocampus may induce cognitive dysfunction by upregulation of TRPM2 in septic mice astrocytes.

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A comparative study of changes of autophagy in rat models of CLP versus LPS induced sepsis

Cited by 6 publications

References 25 publications

RETRACTED: Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy

RETRACTED: Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy

Protective effect of emodin on intestinal epithelial tight junction barrier integrity in rats with sepsis induced by cecal ligation and puncture

IL-1β regulates TRPM2 channel in astrocytes and aggravates their apoptosis during lipopolysaccharide induced cognitive impairment in mice

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