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Buxu Tongyu Granule Alleviates myocardial ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

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Engineering 2024年第7期38卷 133-143页

作者： Shuang Yang Yixiu Zhao Xiaoling Cheng Tingting Zhan Jiaying Tian Xue Liu Chunyue Ma Zhiqi Wang Luying Jin Qian Liu Yanli Wang Jian Huang Jinhui Wang Yan Zhang Baofeng Yang Department of Pharmacology&Key Laboratory of Cardiovascular Medicine Research Ministry of Education of the People’s Republic of ChinaCollege of PharmacyHarbin Medical UniversityHarbin 150081China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Harbin Medical UniversityHarbin 150081China Department of Medicinal Chemistry and Natural Medicine Chemistry College of PharmacyHarbin Medical UniversityHarbin 150081China Research Unit of Noninfectious Chronic Diseases in Frigid Zones Chinese Academy of Medical SciencesHarbin 150081China

myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main *** Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ***,the underlying mechanism of BXTY is still *** this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the *** was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of *** results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma *** addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent *** effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT ***,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of *** expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with *** 2028,ODQ,or KT 5823 also reversed this effect of *** conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

关键词： myocardial ischemia Vasomotion Soluble guanylate cyclase Buxu Tongyu Granule

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Inhibition of SLC26A4 regulated by electroacupuncture suppresses the progression of myocardial ischemia-reperfusion injury

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BIOCELL 2024年第4期48卷 665-675页

作者： FEI KONG QIYUAN TIAN BINGLIN KUANG LILI SHANG XIAOXIAO ZHANG DONGYANG LI YING KONG Department of Endocrinology Heilongjiang University of Chinese MedicineHarbin150040China Department of Cardiology Heilongjiang University of Chinese MedicineHarbin150040China College of Clinical Medicine Heilongjiang University of Chinese MedicineHarbin150040China Department of Nephrology Beijing Hospital of Integrated Traditional Chinese and Western MedicineBeijing100039China College of Acupuncture and Massage Heilongjiang University of Chinese MedicineHarbin150040China Department of Acupuncture Heilongjiang University of Chinese MedicineHarbin150040China

Introduction:myocardial ischemia-reperfusion(IR)injury has received widespread attention due to its damaging ***(EA)pretreatment has preventive effects on myocardial IR ***26A4 is a Na+independent anion reverse transporter and has not been reported in myocardial IR ***:Toﬁnd potential genes that may be regulated by EA and explore the role of this gene in myocardial IR ***:RNA sequencing and bioinformatics analysis were performed to obtain the differentially expressed genes in the myocardial tissue of IR rats with EA *** infarction size was detected by TTC *** CK,creatinine kinase-myocardial band,Cardiac troponin I,and lactate dehydrogenase levels were determined by *** effect of SLC26A4 on cardiomyocyte apoptosis was explored by TUNEL staining and western *** effects of SLC26A4 on inﬂammation were determined by HE staining,ELISA,and real-time *** effect of SLC26A4 on the NF-κB pathway was determined by western ***:SLC26A4 was up-regulated in IR rats but downregulated in IR rats with EA *** with IR rats,those with SLC26A4 knockdown exhibited improved cardiac function according to decreased myocardial infarction size,reduced serum LDH/CK/CK-MB/cTnI levels,and elevated left ventricular ejection fraction and fractional ***26A4 silencing inhibited myocardial inﬂammation,cell apoptosis,phosphorylation,and nuclear translocation of NF-κB ***:SLC26A4 exhibited promoting effects on myocardial IR injury,while the SLC26A4 knockdown had an inhibitory effect on the NF-κB *** results further unveil the role of SLC26A4 in IR injury.

关键词： myocardial ischemia Reperfusion SLC26A4 NF-κB pathway

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Efficacy of Danlou tablet(丹蒌片)on myocardial ischemia/reperfusion injury assessed by network pharmacology and experimental verification

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Journal of Traditional Chinese Medicine 2024年第1期44卷 131-144页

作者： YANG Ye CHEN Xiaoyang YAO Junkai HU Yueyao WANG Wei School of Chinese Medicine Beijing University of Chinese MedicineBeijing 100700China School of Chinese Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China

OBJECTIVE:To investigate the potential pharmacological mechanism of Danlou tablet(丹蒌片,DLT)with a long-term clinical application in the treatment of myocardial ischemia/reperfusion(I/R)injury through network pharmacology,molecular docking and experimental ***:The main chemical ingredients in DLT were retrieved from the Traditional Chinese Medicine(TCM)System Pharmacology Database,the TCM information database,the bioinformatics analysis tool for molecular mechanism of TCM,and HERB *** targets of I/R were accessed from the databases of Online Mendelian Inheritance in Man,Gene Cards,Therapeutic Target Database,and Dis Ge NET *** overlaying genes of DLT and I/R were obtained from the Venny online *** core targets and proteinprotein interaction network were constructed and analyzed via the Search Tool for the Retrieval of Interacting Genes Proteins database and Cytoscape ***,Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by the Metascape *** on the results,the component-target-pathway network was constructed and drafted via the Cytoscape software and the platform of ***,we performed molecular docking to predict the binding information between chemical molecules and target ***,oxygenglucose deprivation/recovery(OGD/R)-induced H9c2 cardiomyocytes were used to validate the results of network pharmacology in ***:A total of 189 active chemical components in DLT and 849 correlative targets of I/R were *** note,133 overlaying genes found from the Venny online platform were concentrated into 28 core ***,the GO and KEGG pathway enrichment analysis presented that DLT might participate in 42 types of GO molecular functions,747 types of GO biological processes,19 types of GO cellular components,and 140 kinds of pathways to treat I/*** the component-targetpathway network,t

关键词： myocardial ischemia reperfusion network pharmacology molecular docking simulation oxygen-glucose deprivation/recovery Danlou tablet

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Diverse Effects of L-arginine on Cardiac Function of Rats Subjected to myocardial ischemia and Reperfusion in vivo

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Acta Biochimica et Biophysica Sinica 2007年第3期39卷 201-207页

作者： Xiaoliang WANG~1 Feng LIANG~2 Xiangying JIAOI Lei LIU~1 Xiaojie BAI~1 Meixia LI~1 Jianmin ZHI~3 Huirong LIU~1* 1 Department of Physiology,Shanxi Medical University,Taiyuan 030001,China 2 Department of Cardiothoracic Surgery,General Hospital of Taiyuan Iron and Steel Company Taiyuan 030003,China 3 Department of Physiology.Shanghai Jiaotong University.College of Basic Medicine,Shanghai 200025,China Department of Physiology Shanxi Medical University Taiyuan 030001 China

In vivo administration of L-arginine at different time points during the course of myocardialischemia and reperfusion（MI/R）has been shown to differentially regulate postischemic *** is one of the most important indexes used to judge the degree of myocardial *** presentstudy attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has adiverse influence on cardiac function of ischemic reperfused hearts and,if so,to investigate the *** adult rats were subjected to 30 min myocardial ischemia followed by 5 h *** L-arginine bolus was given either 10 min before and 50 min after reperfusion（early treatment）or3 h and 4 h after reperfusion（late treatment）.Early treatment with L-arginine markedly increased the leftventricular systolic pressure（LVSP）and dP/dtmax,and decreased myocardial nitrotyrosine *** strictcontrast,late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dtmaxfrom 4 h to 5h after reperfusion,and increase in toxic peroxynitrite formation as measured by *** resultssuggest that the administration of L-arginine at different time points during the course of MI/R leads todiverse effects on cardiac *** supplementation decreased the nitrative stress and improvedleft ventricular ***,late treatment with L-arginine increased the formation of peroxynitriteand aggravated cardiac functional injury.

关键词： myocardial ischemia reperfusion cardiac function nitric oxide peroxynitrite

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A new method for early detection of myocardial ischemia:cardiodynamicsgram(CDG)

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Science China(Information Sciences) 2016年第1期59卷 95-105页

作者： Cong WANG Xunde DONG Shanxing OU Wei WANG Junmin HU Feifei YANG College of Automation Science and Engineering South China University of Technology Department of Radiology General Hospital of Guangzhou Military Command Department 5 of Gerontology General Hospital of Guangzhou Military Command

Early detection of myocardial ischemia via electrocardiographic methods is important and challenging. In the study, based on the standard 12-lead electrocardiography(ECG), a new method called cardiodynamicsgram(CDG) is proposed for early detection of myocardial ischemia. Using a recently proposed deterministic learning algorithm, the cardiodynamics information is extracted from the ST-T segments of standard 12-lead ECG. The CDG is generated by plotting the three-dimensional cardiodynamics information. By analyzing CDG morphology, it is found that significant correlations exist between CDG and ischemia. By evaluating ischemia patients and healthy controls from the Physikalisch-Technische Bundesanstalt(PTB) database and the General Hospital of Guangzhou Military Command, the CDG method achieves a mean sensitivity of 90.3% and a mean specificity of 87.8%, which are higher than those of both the standard 12-lead ECG and the exercise ECG. As it is noninvasive, convenient, and inexpensive, it is hopeful that CDG may become a cost-effective screening method for early detection of ischemic heart diseases.

关键词： early detection myocardial ischemia cardiodynamicsgram(CDG) ECG deterministic learning cardiodynamics

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Traditional Chinese Medicines alleviated myocardial ischemia by regulating Qi and promoting blood circulation

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Journal of Traditional Chinese Medicine 2020年第6期40卷 974-982页

作者： Wang Chen Wang Xiaoreng Tao Tianqi Song Dandan Wang Jianli Wang You Liu Xiuhua Wu Xudong Institute of Basic Theory of Traditional Chinese Medicine China Academy of Chinese Medical ScienceBeijing 100700China Out-patient Department Chinese PLA General HospitalBeijing 100853China Department of Pathophysiology Chinese PLA General HospitalBeijing 100853China

OBJECTIVE:To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ***:Fifty male Wistar rats were randomly divided into five groups(n=10)as follows:(a)sham operation(Sham),(b)myocardial ischemia(Model),(c)treatment that regulates Qi(Qi),(d)treatment that promotes blood circulation(Blood),(e)treatment that both regulates Qi and promotes blood circulation(QB).The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending *** rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 *** parameters were evaluated using open field and elevated plus-maze *** tongue color and sublingual vein were visually *** flow perfusion of tongue and auricle were detected using PIMⅡ.The mesenteric microcirculation was examined via capillaroscopy,and hemodynamics was assessed using a polygraph *** homocysteine(Hcy),creatine kinase isoenzyme(CKMB)levels and endothelin-1(ET-1)were *** and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure,***:Compared with findings in Sham group,rats in model group had coarse hair,dark mucosa of the lips and claw,low activity,and increased *** with findings in Model group,rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual *** were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB *** with findings in Model rats,rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole ***,compared with findings in Model rats,Qi and QB rats exhibited incre

关键词： myocardial ischemia Homocysteine Endothelin-1 Creatine kinase Isoenzymes Qi-stagnation and blood-stasis Regulating Qi and promoting blood circulation

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Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of myocardial ischemia

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Chinese Journal of Integrative Medicine 2022年第4期28卷 319-329页

作者： LU Yan YANG Mei-ling SHEN A-ling LIN Shan PENG Mei-zhong WANG Tian-yi LU Zhu-qing WANG Yi-lian PENG Jun CHU Jian-feng Academy of Integrative Medicine Fujian University of Traditional Chinese MedicineFuzhou350122China Chen Keji Academic Thought Inheritance Studio Fujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative Medicine on Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Acupuncture and Moxibustion Third People’s Hospital Affiliated to Fujian University of Traditional Chinese MedicineFuzhou350122China

Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat ***: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups according to the randomized block design method,and were administered by intragastric administration for 10 consecutive days,and on the 9th and 10th days,rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by *** addition,the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension *** influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ(CaMK Ⅱ)/extracellular regulated protein kinases(ERK)signaling pathway has also been ***: KXA significantly reduced the ISO-induced increase in ST-segment,interventricular septal thickness,cardiac mass index and cardiac tissue pathological changes in ***,the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine(NE)or potassium chloride(KCl)was increased after KXA treatment in an endothelium-independent manner,and was attenuated by preincubation with verapamil,but not with tetraethylammonium chloride,4-aminopyridine,glibenclamide,or barium *** pretreatment attenuated vasoconstriction induced by CaCl_(2)in Ca^(2+)-free solutions containing K^(+) or *** addition,KXA pretreatment inhibited accumulation of Ca^(2+)in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK Ⅱ and p-ERK ***: KXA may inhibit influx and release of calcium and activate the CaMK Ⅱ/ERK signaling pathway to produce vasodilatory effects,thereby improving myocardial injury.

关键词： Kuanxiong Aerosol myocardial ischemia vasodilation Ca^(2+) CaMKⅡ/ERK pathway

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SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury

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Chinese Medical Journal 2023年第20期136卷 2496-2507页

作者： Yuanyuan Luo Shuaishuai Zhou Tao Xu Wanling Wu Pingping Shang Shuai Wang Defeng Pan Dongye Li Department of Cardiology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu 221006China Institute of Cardiovascular Disease Research Xuzhou Medical UniversityXuzhouJiangsu 221002China

Background:Sarcoplasmic reticulum calcium ATPase 2a(SERCA2a)is a key protein that maintains myocardial Ca2+*** present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation(small ubiquitinlike modifier)process after ischemia/reperfusion injury(I/RI)in vitro and in ***:Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout(KO)and wildtype mice with I/RI were ***-relevant protein expression and localization were detected by quantitative real-time PCR(RT-qPCR),Western blotting,and immunofluorescence in vitro and in ***2a-SUMOylation,infarct size,and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes,were detected by immunoprecipitation,triphenyltetrazolium chloride(TTC)-Evans blue staining,and echocardiography ***:The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO+I/RI ***1 and Senp2 messenger ribose nucleic acid(mRNA)and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/***,the highest levels in HL-1 cells were recorded at 12 ***2 expression increased in the cytoplasm,unlike that of *** of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline,reduced the infarction area,and improved cardiac function,while inhibition of Senp1 protein could not restore the above ***:I/RI activated Senp1 and Senp2 protein expression,which promoted Serca2a-deSUMOylation,while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.

关键词： myocardial ischemia Reperfusion injury Sarcoplasmic reticulum calcium-transporting ATPases Sentrin/SUMOspecific protease Calcium overload

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Effects of electroacupuncture on cardiac and gastric activities in acute myocardial ischemia rats

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World Journal of Gastroenterology 2008年第42期14卷 6496-6502页

作者： Shu-Bin Wang Shu-Ping Chen Yong-Hui Gao Jun-Ling Liu Ming-Fu Luo Department of Acu-moxibustion GeneralHospital of Coal Beijing 100028 China Department of Physiology Institute of Acu-moxibustion China Academy of Chinese Medical Sciences Beijing 100700 China Department of Anatomy Institute of Acu-moxibustion China Academy of Chinese Medical SciencesBeijing 100700 China

AIM： To observe the effect of electroacupuncture （EA） of ＂Neiguan＂（PC6） and ＂Gongsun＂（SP4） on pathological changes of the heart and stomach in rats with acute myocardial ischemia （AMI）, and to explore its underlying mechanism. METHODS： Fifty Wistar rats were randomized into control, model, PC6, SP4 and PC6 ＋ SP4 groups （n = 8 each group）. An AMI model was established by occlusion of the descending anterior branch （DAB） of the left coronary artery. ECG-ST of cervico-thoracic lead and electrogastrogram （EGG） were recorded. EA was applied to PC6, SP4 and PC6 ＋ SP4 groups, respectively. At the end of experiments, the rats were transcardicalty perfused with 4% paraformaldehyde, and the heart base myocardium, gastric antrum and duodenum tissues were sampled, sectioned and stained with a reduced form of nicotinamideadenine dinucleotide phosphate （NADPH）-diaphorase histochemical method for displaying nitric oxide synthase （NOS） activity. RESULTS： After AMI, ECG-ST values elevated. After EA, the elevated ECG-ST values at 20 min in PC6group, at 30 min in PC6 ＋ SP4 and SP4 groups had no significant differences in comparison with their respective basal values before AMI. Following AMI, the amplitude and frequency of slow waves of EGG decreased remarkably （P 〈 0.05）. At 30 min after EA, the mean amplitude and frequency of slow waves of EGG in the three EA groups had no marked differences compared with their individual basal levels and those in the control group. After AMI, the mean integral grey values of NOS-positive product in myocardium, gastric antrum and duodenum tissues in the model group increased remarkably in comparison with the control group, while those in three EA groups were lower than those in the model group. No significant differences were found in ECG-ST and EGG improvement among the three EA groups. However, EA of PC6 had a better effect on ECG-ST and EA of PC4 had a better effect on EGG, respectively. CONCLUSION： EA of PC6, SP4 and PC6 ＋ SP4 can significantl

关键词： Electroacupuncture myocardial ischemia ECG-ST Electrogastrogram Heart base Gastricantrum Duodenum Nitric oxide synthase expression

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Protective effects of Yindanxinnaotong capsule in a rat model of myocardial ischemia/reperfusion injury

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Journal of Traditional Chinese Medicine 2014年第6期34卷 699-709页

作者： Wandan Wang Lan Wang Hongjun Yang Jianlu Wang Xiaojie Yin Haiyu Xu Long Cheng Rixin Liang Pharmacology and Pharmacokinetics Laboratory Institute of Chinese MaterialMedical China Academy of Chinese Medical Sciences Institute of Medical Plant Development Chinese Academy of Medical Sciences

OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying ***: myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western ***: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was ***: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the

关键词： myocardial ischemia Reperfusion Components compatibility Yindanxinnaotong cap-sule

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