scholarly journals Dexmedetomidine Ameliorates Lung Injury Induced by Intestinal Ischemia/Reperfusion by Upregulating Cannabinoid Receptor 2, Followed by the Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Meng Chen ◽  
Xue-Tao Yan ◽  
Li Ye ◽  
Jun-Jiao Tang ◽  
Zong-Ze Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Receptor Antagonist ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Akt Pathway ◽  
High Morbidity ◽  
Protective Effects ◽  
Sod Activity ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia/reperfusion (I/R) is a clinical emergency, which often causes lung injury with high morbidity and mortality. Although dexmedetomidine has been identified to have a protective effect on lung injury caused by intestinal I/R, its specific mechanism is still elucidated. In recent years, the cannabinoid (CB2) receptor pathway has been found to be involved in I/R injury of some organs. In the current study, we investigated whether the CB2 receptor pathway contributes to the protective effect of dexmedetomidine on the intestinal I/R-induced lung injury in rats. Dexmedetomidine treatment upregulated the expression of CB2 receptor and suppressed the I/R-induced increases in lung injury scores, inflammatory cell infiltration, lung wet/dry ratio, MPO activity, MDA level, inflammatory cytokines, and caspase-3 expression while augmenting SOD activity and Bcl-2 expression, indicating attenuation of lung injury. Dexmedetomidine treatment also increased the expression of Akt. The protective effects of dexmedetomidine treatment were reversed by the CB2 receptor antagonist AM630 or the PI3K inhibitor wortmannin. And the CB2 receptor antagonist AM630 also downregulated the expression of Akt. Thus, our findings suggest that treatment with dexmedetomidine provides a protective role against lung injury caused by intestinal I/R in rats, possibly due to the upregulation of the CB2 receptor, followed by the activation of the PI3K/Akt pathway.

scholarly journals Irisin Contributes to the Hepatoprotection of Dexmedetomidine during Intestinal Ischemia/Reperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Fan ◽  
Juan Du ◽  
Mao-Hua Wang ◽  
Jia-Man Li ◽  
Bo Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Neutralizing Antibody ◽  
Inflammasome Activation ◽  
High Morbidity ◽  
Antibody Treatment ◽  
Sod Activity ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia/reperfusion (I/R), which is associated with high morbidity and mortality, is also accompanied with abnormal energy metabolism and liver injury. Irisin, a novel exercise-induced hormone, can regulate adipose browning and thermogenesis. The following study investigated the potential role of dexmedetomidine in liver injury during intestinal I/R in rats. Adult male Sprague–Dawley rats underwent occlusion of the superior mesenteric artery for 90 min followed by 2 h of reperfusion. Dexmedetomidine or irisin-neutralizing antibody was intravenously administered for 1 h before surgery. The results demonstrated that severe intestine and liver injuries occurred during intestinal I/R as evidenced by pathological scores and an apparent increase in serum diamine oxidase (DAO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. In addition, the hepatic irisin, cleaved caspase-3, Bax, and NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1), protein expressions, apoptotic index, reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 levels increased; however, the serum irisin level and hepatic Bcl-2 protein expression and superoxide dismutase (SOD) activity decreased after intestinal I/R. Interestingly, dexmedetomidine could reduce the above listed changes and increase the irisin levels in plasma and the liver in I/R rats. Dexmedetomidine-mediated protective effects on liver injury and NLRP3 inflammasome activation during intestinal I/R were partially abrogated via irisin-neutralizing antibody treatment. The results suggest that irisin might contribute to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion.

Protective effect of carnosol on lung injury induced by intestinal ischemia/reperfusion

Surgery Today ◽  
2010 ◽  
Vol 40 (9) ◽  
pp. 858-865 ◽  
Author(s):  
Xiao-Feng Tian ◽  
Ji-Hong Yao ◽  
Xue-Song Zhang ◽  
Shu-Sen Zheng ◽  
Xin-Hua Guo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Intestinal Ischemia Reperfusion

scholarly journals The protective effects of rapamycin on intestinal ischemia/reperfusion induced remote lung injury in mice

2014 ◽  
Vol 7 (1) ◽  
pp. 40a-40a
Author(s):  
Takaya Iida ◽  
Yuji Naito ◽  
Tomohisa Takagi ◽  
Kazuhiro Katada ◽  
Katsura Mizushima ◽  
...  
Keyword(s):  
Lung Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Intestinal Ischemia Reperfusion

scholarly journals Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

2020 ◽  
Vol 21 (16) ◽  
pp. 5799
Author(s):  
Muhammad Tahir ◽  
Samina Arshid ◽  
Belchor Fontes ◽  
Mariana S. Castro ◽  
Simone Sidoli ◽  
...  
Keyword(s):  
Protective Effect ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Morbidity ◽  
Ischemia And Reperfusion ◽  
Cellular Functions ◽  
Regulation Mechanisms ◽  
And Migration ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia reperfusion injury (iIRI) is a severe clinical condition presenting high morbidity and mortality worldwide. Some of the systemic consequences of IRI can be prevented by applying ischemic preconditioning (IPC), a series of short ischemia/reperfusion events preceding the major ischemia. Although neutrophils are key players in the pathophysiology of ischemic injuries, neither the dysregulation presented by these cells in iIRI nor the protective effect of iIPC have their regulation mechanisms fully understood. Protein phosphorylation, as well as the regulation of the respective phosphatases and kinases are responsible for regulating a large number of cellular functions in the inflammatory response. Moreover, in previous work we found hydrolases and transferases to be modulated in iIR and iIPC, suggesting the possible involvement of phosphatases and kinases in the process. Therefore, in the present study, we analyzed the phosphoproteome of neutrophils from rats submitted to mesenteric ischemia and reperfusion, either submitted or not to IPC, compared to quiescent controls and sham laparotomy. Proteomic analysis was performed by multi-step enrichment of phosphopeptides, isobaric labeling, and LC-MS/MS analysis. Bioinformatics was used to determine phosphosite and phosphopeptide abundance and clustering, as well as kinases and phosphatases sites and domains. We found that most of the phosphorylation-regulated proteins are involved in apoptosis and migration, and most of the regulatory kinases belong to CAMK and CMGC families. An interesting finding revealed groups of proteins that are modulated by iIR, but such modulation can be prevented by iIPC. Among the regulated proteins related to the iIPC protective effect, Vamp8 and Inpp5d/Ship are discussed as possible candidates for control of the iIR damage.

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