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Exploring the mechanism of icariin in regulat⁃ing cardiac microvascular endothelial cells based on network pharmacology,molecular docking and in vitro experiments
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作者 CAO Ce LI Li +2 位作者 WANG Ziyan LI Haoran LIU Jianxun 《中国药理学与毒理学杂志》 CAS 北大核心 2023年第S01期25-26,共2页
OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment t... OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment to construct a myocardial ischemiareperfusion model,and were divided into normal,model,low(10μmol·L^(-1)),medium(20μmol·L^(-1))and high(40μmol·L^(-1))ICA group,and high ICA+inhibitor group(40μmol·L^(-1)+20 nmol·L^(-1)).CCK-8 assay was used to assess the protective ability of ICA against CMEC,and cell migration assay and tube-formation assay were used to detect the migration and generation ability of CMEC.The TCMSP database,Swiss-Target database and literature mining methods were used to col⁃lect ICA-related targets,the GeneCards data⁃base was used to collect target genes related to myocardial ischemia/reperfusion,and Cytoscape 3.8.0 software was used to construct a"drug-tar⁃get-disease"network.The potential targets were imported into STRING 11.5 database to obtain the PPI network.GO and KEGG enrichment analyses were performed on the potential targets using the DAVID database.Molecular docking was performed using AutoDock-vina 1.1.2 soft⁃ware.Western blot detected the expression of related proteins.RESULTS After CMEC was subjected to OGD/R treatment,ICA had a protec⁃tive effect at 10^(-1)60μmol·L^(-1);the results of the cell migration assay showed that each group of ICA could promote the migratory effect of CMEC(P<0.01,P<0.01);and the results of tube-for⁃mation assay showed that each group of ICA could significantly promote the generation of branches(P<0.01)and the capillary length exten⁃sion(P<0.05).Network pharmacology collected a total of 23 ICA action targets,1500 disease tar⁃gets and 12 key targets.GO function enrichment analysis found 85 results.KEGG pathway enrich⁃ment analysis found 53 results,involving AGERAGE signaling pathway,sphingolipid signaling pathway and VEGF signaling pathway.Molecu⁃lar docking results showed that ICA had better binding with core targets PRKCB,PRKCA and PTGS2.Western blot results showed that ICA could regulate the expression of PRKCB,PRKCA and PTGS2 proteins.The results of cell migra⁃tion assay,tube-formation assay and protein expression were reversed after addition of PKC inhibitor.CONCLUSION The potential mecha⁃nism of action of ICA against myocardial isch⁃emia-reperfusion injury may be related to the reg⁃ulation of processes such as CMEC migration and angiogenesis,and it functions through the key target gene PKC. 展开更多
关键词 ICARIIN myocardial ischemia-reperfusion injury cardiac microvascular endothelial cells network pharmacology molecular docking
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Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway 被引量:2
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作者 CAO Ce QI Yu-tong +5 位作者 WANG Ao-ao WANG Zi-yan LIU Zi-xin MENG Hong-xu LI Lei LIU Jian-xun 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2023年第12期1066-1076,共11页
Objective:To explore the protective effect of Huoxin Pill(HXP)on acute myocardial ischemia-reperfusion(MIRI)injury in rats.Methods:Seventy-five adult SD rats were divided into the sham-operated group,model group,posit... Objective:To explore the protective effect of Huoxin Pill(HXP)on acute myocardial ischemia-reperfusion(MIRI)injury in rats.Methods:Seventy-five adult SD rats were divided into the sham-operated group,model group,positive drug group(diltiazem hydrochloride,DH),high dose group(24 mg/kg,HXP-H)and low dose group(12 mg/kg,HXP-L)of Huoxin Pill(n=15 for every group)according to the complete randomization method.After 1 week of intragastric administration,the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h.Serum was separated and the levels of creatine kinase(CK),creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH),superoxide dismutase(SOD),and malondialdehyde(MDA),hypersensitive C-reactive protein(hs-CRP)and interleukin-1β(IL-1β)were measured.Myocardial ischemia rate,myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride(TTC).Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN)databases were used to screen for possible active compounds of HXP and their potential therapeutic targets;the results of anti-inflammatory genes associated with MIRI were obtained from GeneC ards,Drugbank,Online Mendelian Inheritance in Man(OMIM),and Therapeutic Target Datebase(TTD)databases was performed;Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment were used to analyze the intersected targets;molecular docking was performed using AutoD ock Tools.Western blot was used to detect the protein expression of Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NFκB)/NOD-like receptor protein 3(NLRP3).Results:Compared with the model group,all doses of HXP significantly reduced the levels of LDH,CK and CK-MB(P<0.05,P<0.01);HXP significantly increased serum activity of SOD(P<0.05,P<0.01);all doses of HXP significantly reduced the levels of hs-CRP and IL-1β(P<0.05,P<0.01)and the myocardial infarction rate and myocardial no-reflow rate(P<0.01).GO enrichment analysis mainly involved positive regulation of gene expression,extracellular space and identical protein binding,KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis.Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4,NFκB and NLRP3 molecules.The protein expressions of TLR4,NFκB and NLRP3 were reduced in the HXP group(P<0.01).Conclusions:HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats,and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4/NFκB/NLRP3 signaling pathway. 展开更多
关键词 Houxin Pill myocardial ischemia-reperfusion injury TLR4/NFκB/NLRP3 signaling pathway network pharmacology molecular docking
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Panax notoginseng Saponins Protect Kidney from Diabetes by Up-regulating Silent Information Regulator 1 and Activating Antioxidant Proteins in Rats 被引量:11
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作者 杜月光 汪丽佩 +2 位作者 钱俊文 章科娜 柴可夫 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2016年第12期910-917,共8页
Objective: To explore the mechanism of the protective effects of Panax notoginseng saponins(PNS) on kidney in diabetic rats. Methods: Diabetic rat model was obtained by intravenous injection of alloxan, and the ra... Objective: To explore the mechanism of the protective effects of Panax notoginseng saponins(PNS) on kidney in diabetic rats. Methods: Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg·day) and PNS-200 mg/(kg·day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7(BMP-7). Silent information regulator 1(SIRT1) was silenced in rat mesangial cells by RNA interference. The mR NA expressions of SIRT-1, monocyte chemoattractant protein-1(MCP-1), transforming growth factor β1(TGF-β1) and plasminogen activator inhibitor-1(PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB(NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde(MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase(SOD) was detected by the classical method of nitrogen and blue four. Results: In diabetic model rats, PNS could not only reduce blood glucose and lipid(P〈0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1(P〈0.01) and in turn suppress the transcription of TGF-β1(P〈0.05) and MCP-1(P〈0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated(P〈0.05) and SOD was up-regulated(P〈0.01), which were both induced by SIRT1 up-regulation. Conclusions: PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins. 展开更多
关键词 Panax notoginseng saponins diabetic nephropathy inflammation nuclear factor κB silent information regulator 1 Chinese medicine
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近10年针刺实验鼠的时-效研究述评
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作者 鲁海 胡佳慧 +3 位作者 韩李莎 张春红 王煜 吴江昀(翻译) 《Journal of Acupuncture and Tuina Science》 CSCD 2020年第4期315-320,共6页
目的:总结针刺干预不同疾病模型鼠相关时间因素对针刺效应的影响规律,为针灸临床提供参考.方法:检索近10年针刺干预实验鼠的有关时-效研究文献,对不同的针刺介入时机、针刺时刻、施术时间、留针时间、针刺间隔时间及疗程等关键时间因素... 目的:总结针刺干预不同疾病模型鼠相关时间因素对针刺效应的影响规律,为针灸临床提供参考.方法:检索近10年针刺干预实验鼠的有关时-效研究文献,对不同的针刺介入时机、针刺时刻、施术时间、留针时间、针刺间隔时间及疗程等关键时间因素与针刺效应的关系进行分析总结.结果:从量学主流观点看,针刺介入时间越早越好;不同疾病模型和不同腧穴的施针时刻应有不同;针刺施术时间,最佳参数总体差异性较大,因病而异;留针时间多在20-30 min;针刺频次多为1次/日;疗程的长短多根据经验确定.结论:纵观针刺干预实验鼠的时-效研究,定论不一,尤其缺乏对于针刺施术时间、针刺频次以及针刺疗程与最佳刺激量的量化研究.今后的研究应探索确定影响针刺干预效果的最佳时间量学参数,是针刺时-效研究的关键和目标,尤应加强对单一疾病(优势病种)全程的独立的针刺时-效研究,以指导临床和学科发展. 展开更多
关键词 针刺疗法 针灸效应 针灸原理 留针 剂量效应关系 针灸 疗程 大鼠 小鼠
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