Qingchang Mixture Prevents the Intestinal Ischemia-reperfusion Injury Through TLR4/NF-kB Pathway

Abstract Background: This study was performed to determine the protection and molecular responses of Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury.Methods: The rat intestinal IR model was prepared. Intestinal ischemic injury was evaluated by the HE staining, biochemical assay and western blot. In addition, human intestinal epithelial cells (IEC-6) hypoxia-reoxygenation (HR) in vitro model was prepared. The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as the small molecule inhibitor of TLR4 or NF-κB.Results: Compared with the IR group, the pretreatment of Qingchang mixture relieved the morphological damage, oxidative stress, inflammatory response and barrier function damage of small intestine tissue. IR significantly increased the expression of TLR4 and NF-κB, while the pretreatment of Qingchang mixture inhibited the expression of TLR4 and NF-κB. Furthermore, the pretreatment of Qingchang mixture, TAK242 or PDTC effectively improved the viability, and hindered apoptosis of the HR-induced IEC-6 cells.Conclusions: Chinese medicine Qingchang mixture prevents the intestinal IR injury through TLR4/NF-kB pathway.

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Omega-3 polyunsaturated fatty acids inhibit the increase in cytokines and chemotactic factors induced in vitro by lymph fluid from an intestinal ischemia-reperfusion injury model

Nutrition ◽

10.1016/j.nut.2014.10.015 ◽

2015 ◽

Vol 31 (3) ◽

pp. 508-514 ◽

Cited By ~ 15

Author(s):

Rui Zhang ◽

Gui-zhen He ◽

Yu-kang Wang ◽

Kai-guo Zhou ◽

En-ling Ma

Keyword(s):

Fatty Acids ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Omega 3 ◽

Injury Model ◽

Chemotactic Factors ◽

Lymph Fluid ◽

Intestinal Ischemia Reperfusion

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miR-381-3p knockdown improves intestinal epithelial proliferation and barrier function after intestinal ischemia/reperfusion injury by targeting nurr1

Cell Death and Disease ◽

10.1038/s41419-018-0450-z ◽

2018 ◽

Vol 9 (3) ◽

Cited By ~ 14

Author(s):

Liwei Liu ◽

Jihong Yao ◽

Zhenlu Li ◽

Guo Zu ◽

Dongcheng Feng ◽

...

Keyword(s):

Reperfusion Injury ◽

Barrier Function ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intestinal Epithelial ◽

Epithelial Proliferation ◽

Intestinal Ischemia Reperfusion

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Hydrogen-rich saline protects intestinal epithelial tight junction barrier in rats with intestinal ischemia–reperfusion injury by inhibiting endoplasmic reticulum stress-induced apoptosis pathway

Journal of Pediatric Surgery ◽

10.1016/j.jpedsurg.2020.01.061 ◽

2020 ◽

Vol 55 (12) ◽

pp. 2811-2819

Author(s):

Shuai Jiang ◽

Qizhong Fan ◽

Ming Xu ◽

Fengchun Cheng ◽

Zhihui Li ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intestinal Epithelial ◽

Apoptosis Pathway ◽

Epithelial Tight Junction ◽

Induced Apoptosis ◽

Intestinal Ischemia Reperfusion

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Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats

Clinical Science ◽

10.1042/cs20160799 ◽

2017 ◽

Vol 131 (8) ◽

pp. 759-773 ◽

Cited By ~ 21

Author(s):

Dongcheng Feng ◽

Jihong Yao ◽

Guangzhi Wang ◽

Zhenlu Li ◽

Guo Zu ◽

...

Keyword(s):

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ros Generation ◽

Mitochondrial Apoptosis ◽

Prolyl Isomerase ◽

Apoptotic Pathway ◽

Apoptosis Pathway ◽

Intestinal Ischemia Reperfusion

Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor 66 kDa isoform of the adaptor molecule ShcA (p66Shc)-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, peptidyl–prolyl cis–trans isomerase (Pin1), in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intraperitoneally before I/R challenge. Caco-2 cells were exposed to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. We found that p66Shc was significantly up-regulated in the I/R intestine and that this up-regulation resulted in the accumulation of intestinal mitochondrial reactive oxygen species (ROS) and massive epithelial apoptosis. Moreover, intestinal I/R resulted in elevated protein expression and enzyme activity of Pin1 as well as increased interaction between Pin1 and p66Shc. This Pin1 activation was responsible for the translocation of p66Shc to the mitochondria during intestinal I/R, as Pin1 suppression by juglone or siRNA markedly blunted p66Shc mitochondrial translocation and the subsequent ROS generation and cellular apoptosis. Additionally, Pin1 inhibition alleviated gut damage and secondary lung injury, leading to improvement of survival after I/R. Collectively, our findings demonstrate for the first time that Pin1 inhibition protects against intestinal I/R injury, which could be partially attributed to the p66Shc-mediated mitochondrial apoptosis pathway. This may represent a novel prophylactic target for intestinal I/R injury.

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Investigating Closed Room Conspirators of Posttraumatic Inflammatory Response: Multi- Omics Profiles of Exosomes Derived from Intestinal Epithelial Cells Under Ischemia Reperfusion Injury

10.21203/rs.3.rs-792334/v1 ◽

2021 ◽

Author(s):

Atsushi Senda ◽

Mitsuaki Kojima ◽

Arisa Watanabe ◽

Tetsuyuki Kobayashi ◽

Keita Nakatsutsumi ◽

...

Keyword(s):

Epithelial Cells ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Intestinal Epithelial Cells ◽

Ischemia Reperfusion ◽

Multiple Organ ◽

Intestinal Epithelial ◽

Intestinal Ischemia Reperfusion

Abstract Intestinal ischemia-reperfusion injury leads to multiple organ injuries via gut-derived mediators following severe injury. Growing evidence suggests that exosomes secreted from intestinal epithelial cells are heavily involved in the development of systemic inflammation, but a full elucidation of its pathology remains to be completed. To produce an integrated understanding of its pathology, this study aimed to reveal the changes in exosome content after ischemic stimulation. Our result showed (1) the proteins involved in inflammation by catalyzing RNAs were upregulated, (2) hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-30d-5p levels were increased while hsa-miR-124-3p level was decreased, (3) the increase in unsaturated lysophosphatidylcholines levels. These results together with those of previous studies, suggest that lysophosphatidylcholines may activate the NK-κB pathway. The proteins and microRNAs jointly act to disrupt negative feedback, thereby increasing inflammation. Thus, our results clarify part of the mechanism of multi-organ failure after intestinal ischemic recanalization, thereby providing a new target for treatment.

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