scholarly journals Senkyunolide I Protects Against Sepsis-associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

2020 ◽  
Author(s):  
Jian Xie ◽  
Zhen-zhen Zhao ◽  
Peng Li ◽  
Cheng-long Zhu ◽  
Yu Guo ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Dysfunction ◽  
Murine Model ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Tunel Staining ◽  
Cecal Ligation And Puncture ◽  
Inflammatory Signaling ◽  
Tnf Α ◽  
Senkyunolide I

Abstract Background: Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide sedative effect to improve sleep. But its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP).Methods: The male C57BL/6 mice were used to investigate the effects of Senkyunolide I on SAE. The related protein of the sleep deprivation and inflammatory signaling pathway was detected by western blot. The activation of microglia and the neuronal apoptosis were separately detected by immunofluorescence staining and TUNEL staining.Results: Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6 and IL-1β. A fear conditioning test was performed and the result showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6 and IL-1β, in the hippocampus homogenate. The sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Conclusion: Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

scholarly journals Senkyunolide I Protects against Sepsis-Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jian Xie ◽  
Zhen-zhen Zhao ◽  
Peng Li ◽  
Cheng-long Zhu ◽  
Yu Guo ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Dysfunction ◽  
Murine Model ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Signaling Proteins ◽  
Cecal Ligation And Puncture ◽  
Inflammatory Signaling ◽  
Tnf Α ◽  
Senkyunolide I

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6, and IL-1β. A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, and p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

scholarly journals A New Approach to Monitoring and Evaluation of Cecal Ligation and Puncture Sepsis Model

2021 ◽  
Vol 3 (2) ◽  
pp. 97-106
Author(s):  
Arezou Khosrojerdi ◽  
◽  
Sara Soudi ◽  
Ahmad Zavaran Hosseini ◽  
Seyed Mahmoud Hashemi ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Chemistry ◽  
Cecal Ligation ◽  
Serum Levels ◽  
Cecal Ligation And Puncture ◽  
Inflammatory Status ◽  
Sepsis Model ◽  
Tnf Α ◽  
Systemic Inflammatory Disease ◽  
Tgf Β1

Background: Sepsis is a systemic inflammatory disease in response to the pathogens that leads to vital organ failures the failure of vital organs. Appropriate animal models should be developed to measure the effectiveness of therapeutic methods. Cecal Ligation and Puncture (CLP) is the most widely used methods of creating the sepsis model. Some variables interfere in the creation of the CLP model which terminated to result in an unrepeatable dynamic of the inflammatory responses. The current research, suggests presents the simultaneous study of inflammatory responses in serum and liver as a criterion for determining the inflammatory status of the CLP model. Materials and Methods: CLP model was induced in 15 female C57bl/6 mice. IL-6, TNF-α, IL-10, and TGF-β1 cytokines levels were measured at 24, 48, and 72 hours after CLP induction in both serum and liver tissue by ELISA method. Serum levels of liver enzymes were analyzed by the clinical chemistry analyzer. All studies were performed in healthy mice as well. The results were reported as Mean±SD. Results: The levels of IL-10 and TGF- β1 in the liver is were significantly (P≤0.05) higher than serum. The production of IL-10 and TGF- β1 in the serum and liver reaches its maximum at peaked 24 and 72 hours after CLP induction. The level of TNF-α in the liver is was significantly (P≤0.05) higher than serum with a maximum production 24 hours after CLP induction. Conclusion: Serum is not a good representative of the inflammatory condition in sepsis. Therefore, it is suggested that local inflammatory responses be considered in evaluating the model, and the determination of drug efficacy.

scholarly journals MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

2021 ◽  
Vol 49 (5) ◽  
pp. 117-124
Author(s):  
Wenmei Liang ◽  
Li Guo ◽  
Tonghua Liu ◽  
Song Qin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tunel Staining ◽  
Cecal Ligation And Puncture ◽  
Tnf Α ◽  
Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

scholarly journals Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Li-Li Gao ◽  
Zhi-Hao Wang ◽  
Yu-Hang Mu ◽  
Zuo-Long Liu ◽  
Li Pang
Keyword(s):  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Field Tests ◽  
Tissue Homogenate ◽  
Tunel Staining ◽  
Mice Model ◽  
Anti Inflammatory ◽  
Related Proteins

<b><i>Objective:</i></b> Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation. Emodin has been confirmed to have anti-inflammatory effects. Thus, we sought to investigate the role of Emodin in SAE. <b><i>Methods:</i></b> The cecal ligation and puncture (CLP) method was used for the establishment of SAE in mice model. For treatment of Emodin, intraperitoneal injection of 20 mg/kg Emodin was performed before the surgery. The Morris water maze and open field tests were carried for measurement of cognitive dysfunction. Hematoxylin and eosin staining was for histological analysis of hippocampus. Cell apoptosis of hippocampus neurons was measured by TUNEL staining. Pro-inflammatory and anti-inflammatory cytokines in hippocampus tissue homogenate were evaluated by ELISA. BDNF/TrkB signaling-related proteins (TrkB, p-TrkB, and BDNF), autophagy-related proteins (LC3 II/I and Beclin-1), and apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were detected by Western blotting. <b><i>Results:</i></b> Emodin significantly inhibited apoptosis and induced autophagy in hippocampal neurons of CLP-treated mice. In addition, Emodin significantly ameliorated CLP-induced cognitive dysfunction and pathological injury in mice. Meanwhile, Emodin notably inhibited CLP-induced inflammatory responses in mice via upregulation of BDNF/TrkB signaling, while the effect of Emodin was partially reversed in the presence of K252a (BDNF/TrkB signaling inhibitor). <b><i>Conclusion:</i></b> Emodin significantly inhibited the progression of SAE via mediation of BDNF/TrkB signaling. Thus, Emodin might serve as a new agent for SAE treatment.

scholarly journals IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

2016 ◽  
Vol 38 (6) ◽  
pp. 2163-2172 ◽  
Author(s):  
Xiaorong Hu ◽  
Ruisong Ma ◽  
Jiajia Lu ◽  
Kai Zhang ◽  
Weipan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Tunel Staining ◽  
Ischemia And Reperfusion ◽  
Stress Reactions ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Myocardial Ischemia And Reperfusion ◽  
Tnf Α ◽  
And Oxidative Stress

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

scholarly journals Floroindole confers protection against cecal ligation and puncture-induced sepsis via inhibition of NF-kB p65 phosphorylation

2021 ◽  
Vol 18 (6) ◽  
pp. 1161-1166
Author(s):  
Zhiwen Zhou ◽  
Xiang Ren ◽  
Aiping Li ◽  
Wensheng Zhou ◽  
Li Huang
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
Degree Of Protection ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Factor Α

Purpose: To investigate the protective effect of floroindole against cecal ligation and puncture (CLP)- induced sepsis, as well as the underlying mechanism of action. Methods: Thirty-five 10–week-old male Wistar rats weighing 190 - 210 g (mean: 200.00 ± 10.10 g) were used for this study. The rats were randomly assigned to seven groups of five rats each, viz, normal control group, and six CLP groups. The CLP groups were those subjected to cecal ligation and puncture (CLP). The first 5 CLP groups received 2, 4, 6, 8 or 10 mg/kg floroindole, respectively, 1 h after CLP, via intraperitoneal route (i.p.) while the 6th CLP group served as untreated control. Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) were used for the assessment of the expression levels of tumor necrosis factor-α (TNF- α), interleukn-6 (IL-6), nucleotide-binding oligomerization domain 2 (NOD2) and p-NF-κB p65. Results: Cecal ligation and puncture (CLP) significantly and time-dependently upregulated the expressions of TNF-α, IL-6 and NOD2 in intestinal tissues of rats (p < 0.05). However, treatment with floroindole significantly, and dose-dependently down-regulated CLP-induced expressions of these proteins (p < 0.05). Treatment of rats with floroindole also significantly and dose-dependently inhibited CLP-induced phosphorylation of NF-κB p65 in rat ileum (p < 0.05). Conclusion: The results obtained in this study demonstrate that floroindole confers some degree of protection against CLP-induced sepsis via inhibition of NF-κB p65 phosphorylation.

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