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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway 被引量:1
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作者 Qing-Zhi Hu Zhen-Rui Cao +5 位作者 Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第4期344-352,共9页
Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)funct... Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI. 展开更多
关键词 ischemia-reperfusion injury Liver transplantation INFLAMMATION HSP110 Heat shock proteins NF-ΚB
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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization
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作者 Hai-Li Bao Chuan-Zhi Chen +4 位作者 Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第1期25-34,共10页
Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate w... Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling. 展开更多
关键词 Hepatic ischemia-reperfusion injury POLYDATIN MACROPHAGE POLARIZATION INFLAMMATION
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Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide
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作者 Yan-Xia Wu Shuo Yin +3 位作者 Shan-Shan Song Xiang Liu Yu-Xuan Deng Xue-Jing Lu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第9期1599-1605,共7页
AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through an... AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for 7d.After 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were measured.RESULTS:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model group.Caspase-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model group.Caspase-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model.CONCLUSION:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model. 展开更多
关键词 retinal ischemia-reperfusion Lycium barbarum glycopeptide PRETREATMENT ANTI-INFLAMMATORY ANTIOXIDATIVE RAT
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Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury
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作者 Ya-Kuan Wang Huang Lin +4 位作者 Shu-Rui Wang Ru-Tao Bian Yang Tong Wen-Tao Zhang Ying-Lin Cui 《World Journal of Clinical Cases》 SCIE 2024年第4期688-699,共12页
Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage ... Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice. 展开更多
关键词 Sanhua Decoction Cerebral ischemia-reperfusion Mechanism of action Application progress Traditional Chinese medical science REVIEW
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Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation
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作者 Feng-Dan Wang Yi Ding +8 位作者 Jian-Hong Zhou En Zhou Tian-Tian Zhang Yu-Qi Fan Qing He Zong-Qi Zhang Cheng-Yu Mao Jun-Feng Zhang Jing Zhou 《World Journal of Stem Cells》 SCIE 2024年第10期873-895,共23页
BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whet... BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI. 展开更多
关键词 Extracellular vesicles Myocardial ischemia-reperfusion injury Adipose-derived mesenchymal stem cells Gammaaminobutyric acid Thioredoxin-interacting protein
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Protective Effect of Naringenin on Acute Myocardial Ischemia-reperfusion Injury in Rats
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作者 Xia ZHANG Ping ZHOU +3 位作者 Juan LI Zhaojun XIANG Qianqian LUO Qing DENG 《Medicinal Plant》 2024年第3期50-52,共3页
[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were ran... [Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases. 展开更多
关键词 Rat NARINGENIN Acute myocardial ischemia-reperfusion Lipid PEROXIDATION Inducible/endothelial NITRIC oxide SYNTHASE
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The mechanisms that regulate neuronal pyroptosis in cerebral ischemia-reperfusion injury:current theories and recent advances
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作者 Hui Li Lu Liu +1 位作者 Chen Zhou Xunming Ji 《Journal of Translational Neuroscience》 2024年第1期10-14,共5页
Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While th... Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI. 展开更多
关键词 cerebral ischemia-reperfusion injury PYROPTOSIS connexin 43
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Network pharmacology investigation of the mechanism underlying the therapeutic action of Shikang granules in retinal ischemia-reperfusion injuries
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作者 Xiao-Xuan Wang Cong-Ying Wang +3 位作者 Chi Zhang Fang-Yuan Zheng Long-Hui Han Ming-Lian Zhang 《Integrative Medicine Discovery》 2024年第17期1-8,共8页
Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations ... Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway. 展开更多
关键词 retinal ischemia-reperfusion injury Shikang granules APOPTOSIS PI3K/AKT pathway
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Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury
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作者 Hang Yang Yulei Xia +4 位作者 Yue Ma Mingtong Gao Shuai Hou Shanshan Xu Yanqiang Wang 《Neural Regeneration Research》 SCIE CAS 2025年第7期1900-1918,共19页
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie... The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury. 展开更多
关键词 calcium homeostasis cellular autophagy cerebral ischemia-reperfusion injury cGAS–STING pathway ferroptosis gut–brain–microbiota axis inflammatory light chain 3 microglial cells Syntaxin-17 protein
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Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury 被引量:5
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作者 Shan-Fei Zhu Wei Yuan +1 位作者 Yong-Liang Du Bai-Lin Wang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2023年第1期45-53,共9页
Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding R... Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets. 展开更多
关键词 NCRNA lncRNA MIRNA Hepatic ischemia-reperfusion injury Research progress
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Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury 被引量:1
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作者 Yi-Chao Wang Meng-Jun Wu +1 位作者 Sheng-Liang Zhou Zhi-Hui Li 《World Journal of Clinical Cases》 SCIE 2023年第3期487-492,共6页
Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and ... Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs. 展开更多
关键词 HSK3486 THERAPEUTIC Cerebral ischemia-reperfusion injury HYPOTHESIS
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Improved methodology for efficient establishment of the myocardial ischemia-reperfusion model in pigs through the median thoracic incision 被引量:1
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作者 Liuhua Zhou Jiateng Sun +14 位作者 Tongtong Yang Sibo Wang Tiankai Shan Lingfeng Gu Jiawen Chen Tianwen Wei Di Zhao Chong Du Yulin Bao Hao Wang Xiaohu Lu Haoliang Sun Meng Lv Di Yang Liansheng Wang 《The Journal of Biomedical Research》 CAS CSCD 2023年第4期302-312,共11页
To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham... To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area. 展开更多
关键词 coronary artery ligation myocardial ischemia-reperfusion injury Bama pig animal model
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Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats 被引量:2
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作者 Jia-Yi Zhan Yao Zhang +3 位作者 Xie Zhong Han Mao Xiang-Yun Chen Yao-Feng Li 《Traditional Medicine Research》 2023年第4期29-37,共9页
Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;howe... Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway. 展开更多
关键词 Liqi Huoxue dripping pill myocardial ischemia-reperfusion injury myocardial injury PI3K/Akt/GSK-3βsignaling pathway
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MELLT3 protects against cerebral ischemia-reperfusion (I/R) injury through up-regulation of m6A modification
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作者 JING JIN XINGHUA WANG +6 位作者 XIAOXIAO ZHENG JIAHUA LAN LI ZHENG YING CAI HUI CHEN HONGWEI WANG LIFANG ZHENG 《BIOCELL》 SCIE 2023年第3期619-626,共8页
Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aime... Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury. 展开更多
关键词 METTL3 m6A Cerebral ischemia-reperfusion
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Non-coding RNAs:The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury
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作者 Jia-Li Shao Li-Juan Wang +1 位作者 Ji Xiao Jin-Feng Yang 《World Journal of Gastroenterology》 SCIE CAS 2023年第33期4927-4941,共15页
Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mec... Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets. 展开更多
关键词 Hepatic ischemia-reperfusion injury Non-coding RNAs MICRORNAS Long non-coding RNAs Circular RNAs
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Exploring the attenuation mechanisms of Dalbergia odorifera leaves extract on cerebral ischemia-reperfusion based on weighted gene co-expression network analysis
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作者 JINFANG HU JIANGEN AO +6 位作者 LONGSHENG FU YAOQI WU FENG SHAO TIANTIAN XU MINGJIN JIANG SHAOFENG XIONG YANNI LV 《BIOCELL》 SCIE 2023年第7期1611-1622,共12页
The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion(I/R)is little known.The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chroma... The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion(I/R)is little known.The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chromatography.The molecular mechanism of D.odorifera leaves on cerebral I/R was investigated.Methods:Serial affinity chromatography based on D.odorifera leaves extract(DLE)affinity matrices were applied to find specific binding proteins in the brain tissues implemented on C57BL/6 mice by intraluminal middle cerebral artery occlusion for 1 h and reperfusion for 24 h.Specific binding proteins were subjected to mass-spectrometry to search for the differentially expressed proteins between control and DLE-affinity matrices.The hub genes were screened based on weighted gene co-expression network analysis(WGCNA).Then,predictive biology and potential experimental verification were performed for the candidate genes.The protective role of DLE in blood-brain barrier damage in cerebral I/R mice was evaluated by the leakage of Evans blue,western blotting,immunohistochemistry,and immunofluorescent staining.Results:952 differentially expressed proteins were classified into seven modules based on WGCNA under soft threshold 6.Based on WGCNA,AKT1,PIK3CA,NOS3,SMAD3,SMAD1,IL6,MAPK1,TGFBR2,TGFBR1,MAPK3,IGF1R,LRG1,mTOR,ROCK1,TGFB1,IL1B,SMAD2,and SMAD518 candidate hub proteins were involved in turquoise module.TGF-β,MAPK,focal adhesion,and adherens junction signaling pathway were associated with candidate hub proteins.Gene ontology analysis demonstrated that candidate hub proteins were related to the TGF-βreceptor signaling pathway,common-partner SMAD protein phosphorylation,etc.DLE could significantly reduce the leakage of Evans blue in mice with cerebral I/R,while attenuating the expression of occludin,claudin-5,and zonula occludens-1.Western blotting demonstrated that regulation of TGF-β/SMAD signaling pathway played an essential role in the protective effect of DLE.Conclusion:Thus,a number of candidate hub proteins were identified based on DLE affinity chromatography through WGCNA.DLE could attenuate the dysfunction of bloodbrain barrier in the TGF-β/SMAD signaling pathway induced by cerebral I/R. 展开更多
关键词 Dalbergia odorifera leaves Serial affinity chromatography WGCNA Cerebral ischemia-reperfusion TGF-β SMADS
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Effect of salvianolic acid B-loaded mesoporous silica nanoparticles on myocardial ischemia-reperfusion injury
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作者 Ming-Juan Yang Xiao-Ying Han +9 位作者 Ou Qiao Hai-Xia Ji Yi Zhang Xin-Yu Zhang Wen-Zhe Wang Xia Li Juan Wang Lan-Ping Guo Lu-Qi Huang Wen-Yuan Gao 《Traditional Medicine Research》 2023年第8期25-36,共12页
Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical app... Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB. 展开更多
关键词 salvianolic acid B myocardial ischemia-reperfusion injury mesoporous silica NANOPARTICLES
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Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog
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作者 Christina Mouratidou Efstathios T Pavlidis +5 位作者 Georgios Katsanos Serafeim-Chrysovalantis Kotoulas Eleni Mouloudi Georgios Tsoulfas Ioannis N Galanis Theodoros E Pavlidis 《World Journal of Gastrointestinal Surgery》 SCIE 2023年第9期1858-1870,共13页
Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections... Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections and liver transplantation.In addition to the organ’s post reperfusion injury,this syndrome appears to play a central role in the dysfunction of distant tissues and systems.Thus,continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates.Treprostinil is a synthetic analog of prostaglandin I2,and its experimental administration has shown encouraging results.It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation,where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min.Treprostinil improves renal and hepatic function,diminishes hepatic oxidative stress and lipid peroxidation,reduces hepatictoll-like receptor 9 and inflammation,inhibits hepatic apoptosis and restores hepatic adenosine triphosphate(ATP)levels and ATP synthases,which is necessary for functional maintenance of mitochondria.Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflam-matory cytokines;therefore,it can potentially minimize ischemia-reperfusion injury.Additionally,it may have beneficial effects on cardiovascular parameters,and much current research interest is concentrated on this compound. 展开更多
关键词 Hepatic ischemia-reperfusion syndrome Myocardial damage PROSTAGLANDINS TREPROSTINIL Liver transplantation HEPATECTOMY
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Atorvastatin Alleviates Myocardial Ischemia-Reperfusion Injury via miR-26a-5p/FOXO1
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作者 Jinlan Duan Tong Zhang +3 位作者 Ying Zhu Bingtuan Lu Qi Zheng Ninghui Mu 《Journal of Biosciences and Medicines》 CAS 2023年第2期215-231,共17页
Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart f... Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart failure, and it is particularly important to seek new strategies to mitigate reperfusion injury. In this paper, we will investigate whether atorvastatin can alleviate myocardial ischemia-reperfusion injury and verify its molecular mechanism. Methods: We successfully constructed a hypoxia-reperfusion (H/R) H9c2 cell model and transfected miR-26a-5p mimic, miR-26a-5p inhibitor and its negative control NC-mimic or NC-inhibitor into H9c2 cells using a transfection kit. The expression of miR-26a-5p and FOXO1 were detected by RT-qPCR assay, the expression of related proteins by Western blot assay, the cell viability of H9c2 cells by CCK-8 assay, the apoptosis rate of H9c2 cells by flow cytometry, the CK and LDH activity in cells by CK and LDH assay kits. The targeting relationship between miR-26a-5p and FOXO1 was verified by dual luciferase reporter gene assay. Results: MiR-26a-5p expression was decreased in H/R-induced cells and FOXO1 expression was increased in H/R-induced cells. Atorvastatin alleviated H/R injury in cardiomyocytes and was most effective at a concentration of 1 μM. Atorvastatin alleviated H/R injury in cardiomyocytes by upregulating miR-26a-5p expression, miR-26a-5p and FOXO1 were negatively regulated by targeting. Conclusion: Atorvastatin can alleviate H/R injury in cardiomyocytes by regulating miR-26a-5p/FOXO1. 展开更多
关键词 Myocardial ischemia-reperfusion Injury ATORVASTATIN miR-26a-5p FOXO1
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Neuroprotective effects of ischemic adaptation on cognitive dysfunction in mice with cerebral ischemia-reperfusion injury
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作者 Yongxin Ma Meng Zhang +3 位作者 Meng Geng Wenjing Zhou Xiuhua Bai Yaoming Xu 《Journal of Translational Neuroscience》 2023年第3期20-27,共8页
Objective: To observe the effects of remote ischemia on cognitive function and neuronal pathological damage in rats with cognitive impairment induced by bilateral common carotid artery occlusion(BCAO).Methods:Male SD ... Objective: To observe the effects of remote ischemia on cognitive function and neuronal pathological damage in rats with cognitive impairment induced by bilateral common carotid artery occlusion(BCAO).Methods:Male SD rats were selected to establish the cognitive impairment model induced by cerebral ischemia reperfusion caused by BCAO.The tests included three groups of rats:a sham group,a model group with vascular cognitive impairment (VCI) , and a remote ischemic conditioning (RIC) group (VCI + RIC group). From 24 h after operation, both hind limbs of rats in VCI + RIC group were treated with RIC. After 28 d, Morris water maze test and HE staining was used to observe the pathological changes of white matter and hippocampus in each group.Results: After 3 d mice in VCI group began to improve gradually. The recovery of rats in the VCI + RIC group was relatively slow,but they started to recover rapidly 2 d after the operation.Morris water maze test showed that the escape latency of rats in VCI group and VCI+RIC group was longer than that in the sham group, and the score of VCI+RIC group was better than that of the VCI group, but there was a significant difference between the two groups(P<0.05).The space exploration experiment was performed at 7 d and 28 d after the operation;the VCI+RIC group outperformed the VCI group in both trials;the difference between the two groups was statistically significant (P<0.05).In the target quadrant exploration time, the difference between the VCI group (33.5±11.3 s) and the VCI+RIC group (41.2±9.7 s) was statistically significant (P<0.05).Results from the hematoxylin and eosin(HE)staining showed that compared with VCI group, cortical cells in VCI + RIC group had loose stroma, thinner nerve fibers, fewer broken cells, and slightly shrunken cells. Compared with VCI group, neurons in VCI + RIC group had a little vacuolar degenera-tion and slightly shrunken cell volume.Conclusion:Cerebral ischemia-reperfusion injury can cause learning and memory impairment in rats, leading to VCI. RIC can significantly improve VCI and play a neuroprotective role. 展开更多
关键词 remote ischemic conditioning cere-bral ischemia-reperfusion cognitive impairment hippo-campal changes NEUROPROTECTION
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