scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

The cardioprotection of dihydrotanshinone I against myocardial ischemia–reperfusion injury via inhibition of arachidonic acid ω-hydroxylase

2016 ◽  
Vol 94 (12) ◽  
pp. 1267-1275 ◽  
Author(s):  
Yidan Wei ◽  
Meijuan Xu ◽  
Yi Ren ◽  
Guo Lu ◽  
Yangmei Xu ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arachidonic acid (AA) is a precursor that is metabolized by several enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia–reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro. The purpose of the present study was to investigate the cardioprotection of DI against MIRI and its effects on the concentrations of 20-HETE in vivo. Rats subjected to 30 min of ischemia followed by 24 h of reperfusion were assigned to intravenously receive vehicle (sham and ischemia–reperfusion), low (1 mg/kg), middle (2 mg/kg), or high (4 mg/kg) doses of DI before reperfusion. The results demonstrated that DI treatment could improve cardiac function, reduce infarct size, ameliorate the variations in myocardial zymogram and histopathological disorders, decrease 20-HETE generation, and regulate apoptosis-related protein in myocardial ischemia–reperfusion rats. These findings suggested DI could exert considerable cardioprotective action on MIRI by the attenuation of 20-HETE generation, subsequent myocardial injury, and apoptosis through inhibition on AA ω-hydroxylase.

scholarly journals Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

2020 ◽  
Author(s):  
Tian Zhang ◽  
Dan Xu ◽  
Fengyang Li ◽  
Rui Liu ◽  
Kai Hou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Caspase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- (5days) and post- (15days) treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R, 2h of ischemia and 24h/15days of reperfusion) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by platelet inhibition induced regulation of the NF-κB/Caspase-1/GSDMD pathway.Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

scholarly journals Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Min Wang ◽  
Rui-ying Wang ◽  
Jia-hui Zhou ◽  
Xue-heng Xie ◽  
Gui-bo Sun ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.

scholarly journals Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

2021 ◽  
Vol 15 (1) ◽  
pp. 1
Author(s):  
Kaili Lin ◽  
Zhang Zhang ◽  
Zhu Zhang ◽  
Peili Zhu ◽  
Xiaoli Jiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Therapeutic Effects ◽  
Gsk 3Β

Oleanolic acid (OA), a bioactive ingredient of Panax ginseng, exhibits neuroprotective pharmacological effects. However, the protective role of OA in cerebral ischemia and involved mechanisms remain unclear. This study attempted to explore the therapeutic effects of OA both in vitro and in vivo. OA attenuated cytotoxicity and overproduction of intracellular reactive oxygen species (ROS) by regulation of glycogen synthase kinase-3β (GSK-3β)/heme oxygenase-1 (HO-1) signal in oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed SH-SY5Y cells. Additionally, OA administration significantly reduced the area of cerebral infarction and the neurological scores in the rat models of cerebral ischemia with middle cerebral artery occlusion (MCAO). The OA administration group showed a higher percentage of Nissl+ and NeuN+ cells, along with lower TUNEL+ ratios in the infarct area of MCAO rats. Moreover, OA administration reduced ROS production while it suppressed the GSK-3β activation and upregulated the HO-1 expression in infarcted tissue. Our results illustrated that OA significantly counteracted cerebral ischemia-mediated injury through antioxidant effects induced by the regulation of the GSK-3β/HO-1 signaling pathway, implicating OA as a promising neuroprotective drug for the therapy of ischemic stroke.

scholarly journals Involvement of GPR30 in protection effect of Dexmedetomidine against myocardial ischemia/reperfusion injury in rat via AKT pathway

2021 ◽  
Author(s):  
Zheming Shao ◽  
Qihong Shen ◽  
Min Kong ◽  
Huadong Ni ◽  
Xiaomin Hou
Keyword(s):  
Protective Effect ◽  
Molecular Mechanism ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Mechanism Analysis ◽  
Protective Effects ◽  
Akt Inhibitor

Acute myocardial infarction (AMI) is a heart disease that seriously threatens human health. Dexmedetomidine (DEX) has a certain protective effect on cardiac injury. This study investigated the cardioprotective effect of DEX and its potential molecular mechanism in vivo and in vitro. The results showed that DEX could significantly increase the viability of hypoxia/reoxygenation (H/R) treated cardiomyocytes and reduce oxidative damage and apoptosis. Further molecular mechanism analysis showed that the above cardiac protective effects may be related to Akt signaling pathway. In addition, the expression of G-Protein Receptor 30 (GPR30) was promoted after H/R treatment. However, knockdown of GPR30 by shRNA significantly counteracted the cardioprotective effect of DEX. Meanwhile, we constructed a rat model of AMI to investigate the role of GPR30 in vivo. The results showed that DEX significantly reduced the infarct size, and GPR30 agonist G1 enhanced the protective effect of DEX on heart. On the contrary, protein kinase B (AKT) inhibitor LY294002 counteracted the protective effect of DEX on heart, suggesting that GPR30 enhanced the protective effect of DEX on ischemia-reperfusion induced heart injury by regulating AKT related pathways. In conclusion, our study provides a potential target for the clinical treatment of AMI.

scholarly journals Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

2020 ◽  
Author(s):  
Tian Zhang ◽  
Dan Xu ◽  
Fengyang Li ◽  
Rui Liu ◽  
Kai Hou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Caspase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- and post-treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

LncRNA Gm4419 induces cell apoptosis in hepatic ischemia–reperfusion injury via regulating the miR-455–SOX6 axis

2020 ◽  
Vol 98 (4) ◽  
pp. 474-483 ◽  
Author(s):  
Dongjian Ying ◽  
Xinhua Zhou ◽  
Yi Ruan ◽  
Luoluo Wang ◽  
Xiang Wu
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Annexin V ◽  
Luciferase Reporter ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Long non-coding RNA (lncRNA) is known to be involved in a variety of diseases. However, the role of Gm4419 in hepatic ischemia–reperfusion (I/R) injury remains unknown. To study this, we first established a rat model of hepatic I/R, and a BRL-3A cell model of hypoxia–reoxygenation (H/R) for in vivo and in vitro studies. Staining with hematoxylin and eosin and hepatic injury scores were used to evaluate the degree of hepatic I/R injury. Cell apoptosis was assessed via staining with Edu, and with annexin V–FITC–propidium iodide assays. The interactions between Gm4419 and miR-455, as well as miR-455 and SOX6 were evaluated via luciferase reporter activity assays and RNA immunoprecipitation assays. In vivo, we found that Gm4419 was up-regulated in the rats subjected to I/R. Moreover, knockdown of Gm4419 alleviated the I/R-induced liver damage in the rats. In vitro, knockdown of Gm4419 alleviated H/R-induced apoptosis in BRL-3A cells. Interestingly, we found that miR-455 is a target of Gm4419, and Gm4419 regulates the expression of miR-455 via sponging. Furthermore, SOX6 was proven to be the target of miR-455. Finally, rescue experiments confirmed that knockdown of Gm4419 inhibits apoptosis by regulating miR-455 and SOX6 in H/R-treated BRL-3A cells. Therefore, our findings show that the lncRNA Gm4419 accelerates hepatic I/R injury by targeting the miR-455–SOX6 axis, which suggests a novel therapeutic target for hepatic I/R injury.

scholarly journals Microglia-derived FGF21 as a modulator of astrocytic phenotype and cerebral ischemia injury

2020 ◽  
Author(s):  
Fei Liu ◽  
Dongxue Wang ◽  
Liyun Zhu ◽  
Jingting Du ◽  
Ping Lin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cell Counting ◽  
Fibroblast Growth Factor 21 ◽  
Protective Effects ◽  
Triphenyltetrazolium Chloride

Abstract Background: Fibroblast growth factor 21 (FGF21) is an important neuroprotective factor in the central nervous system (CNS), and it has been reported that FGF21 can protect against cerebral ischemia during the acute phase. However, the possible effects of FGF21 on ischemic brains and the interactions between FGF21 and nonneuronal cells have not been examined. Thus, the aim of this study was to elucidate the protective effects of endogenous FGF21 in ischemic brains.Methods: In this study, in vivo ischemia/reperfusion injury mouse model established by transient middle cerebral artery occlusion (MCAO)/reperfusion and in vitro cell models of oxygen/glucose deprivation (OGD)/reoxygenation (R) were used. Western blot analysis, RT-PCR, double immunofluorescence staining, immunohistochemistry, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, neurobehavioral tests, cell counting kit-8 (CCK-8) assay and high-throughput gene sequencing were employed to explore the mechanism by which FGF21 unleash neuroprotective effort of astrocyte phenotype shifts in ischemic stroke.Results: We found that cortical FGF21 expression significantly increased after MCAO/reperfusion, peaking at 7 d. Ischemia-activated microglia were the main sources of endogenous FGF21 in brain tissue. However, FGF21 deficiency aggravated brain injury and slowed neurological functional recovery in FGF21 knockout mice. The in vitro and vivo studies revealed that FGF21 could activate astrocytes and mediate astrocytic phenotype. FGF21-activated astrocytes contributed to neuronal survival and synaptic protein upregulation after ischemia.Conclusion: Collectively, our data indicate that FGF21 plays vital roles in alleviating ischemic brain by mediating the manifestation of potentially pro-recovery astrocytic phenotypes. Therefore, modulation of FGF21 is a potential target strategy for stroke.

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