UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Influence of Acupuncture on Microcirculation Perfusion of Pericardium Meridian and Heart in Acute Myocardial Ischemia Model Rats / 中国结合医学杂志

OBJECTIVE@#To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed.@*METHODS@#Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System.@*RESULTS@#After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05).@*CONCLUSIONS@#Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.

Network pharmacology study of Tibetan medicine Corydalis Herba against acute myocardial ischemia / 中国中药杂志

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.

Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area.@*METHODS@#A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining.@*RESULTS@#Compared with the sham-operation group, EF and FS were decreased (@*CONCLUSION@#Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

Gualou-Xiebai-Banxia decoction protects against type II diabetes with acute myocardial ischemia by attenuating oxidative stress and apoptosis via PI3K/Akt/eNOS signaling / 中国天然药物

Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China. In this study, we investigated the protective effect and underlying mechanisms GXB in type II diabetes with acute myocardial ischemia (T2DM-AMI) rats. We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells (EPCs) apoptosisviaactivating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling. Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type II diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI). Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination. The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry. Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis. The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose, muscular enzymes, and blood lipids, and reduced oxidative stress. Furthermore, EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K, Akt, and eNOS compared to the controls. Conversely, T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis, combined with increased mRNA and protein levels of PI3K, Akt, and eNOS compared to those of untreated T2DM-AMI rats. Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.

Effects of electroacupuncture pretreatment on cardiac function and immune inflammatory response in mice with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) pretreatment on the cardiac ejection fraction (EF), the number of macrophages in spleen and heart, and the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in myocardium in mice with acute myocardial ischemia, and to explore the possible mechanism of EA pretreatment on promoting myocardial protection.@*METHODS@#A total of 30 male C57BL/6J mice were randomly divided into a control group, a model group and an EA pretreatment group, 10 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the control group. In the EA pretreatment group, mice were intervented with EA at bilateral "Neiguan" (PC 6), disperse-dense wave, frequency of 2 Hz/15 Hz, intensity of 2 mA; each EA treatment last for 20 min, once a day, and 3-day treatment was given before model establishment. The EF value was evaluated by ultrasonic cardiogram; the number of macrophages in spleen and heart was measured by flow cytometry; the expression level of NLRP3 and IL-1β in myocardium was measured by Western blot.@*RESULTS@#Compared with the control group, the EF value was decreased in the model group (<0.001), the number of macrophages in the heart and spleen was increased (<0.001), and the expression level of NLRP3 and IL-1β in the myocardium was increased (<0.001, <0.01). Compared with the model group, the EF value was increased in the EA pretreatment group (<0.01), the number of macrophages in the heart and spleen was decreased (<0.01), and the expression level of NLRP3 and IL-1β in the myocardium was decreased (<0.01, <0.05).@*CONCLUSION@#EA pretreatment could reduce the number of macrophages in spleen and heart, down-regulate the expression of NLRP3 and IL-1β in myocardial tissue in mice with acute myocardial ischemia, which could relieve the local inflammatory response and achieve the myocardial protective effect.

Effect of Tianlong Tongxin Tablet on Acute Myocardial Ischemia Injury in Dogs / 中国实验方剂学杂志

Objective:To observe the effect of oral administration of Tianlong Tongxin tablet on acute myocardial ischemia and related indexes in experimental dogs. Method:The model of acute myocardial ischemia in dogs was established and the dogs were divided into the control group （equal amount of normo-cyclodintrin 10 g·kg-1）， Hexinshuang group （5 mg·kg-1）， Tianlong Tongxin tablet high， medium and low dose groups （1， 0.5， 0.25 g·kg-1） and the compound Danshen tablet group （0.144 g·kg-1）. Myocardial ischemia degree was measured by epicardium electrocardiogram， the range of myocardial infarction was determined by quantitative histology （N-BT staining）， and coronary blood flow， cardiac output， myocardial oxygen consumption， coronary resistance and peripheral resistance were measured. Meanwhile， serum creatine kinase （CK）， lactate dehydrogenase （LDH） and serum superoxide dismutase （SOD） activity and malondialdehyde （MDA） content were detected by optical kit. Result:As compared with the control group， Tianlong Tongxin tablet can reduce the myocardial ischemia degree （∑-ST） measured by the electrocardiogram of the pericardium （P<0.05）， reduce the infarcted area shown by N-BT staining （P<0.05）， reduce the venous oxygen content （P<0.05）， increase the coronary flow， cardiac output and myocardial oxygen consumption of anesthetized dogs， and reduce the coronary artery resistance and peripheral resistance （P<0.05）. However， there was no significant difference in the influence of serum CK， LDH， SOD activity and MDA content in serum. Conclusion:Tianlong Tongxin tablet can improve acute myocardial ischemia and myocardial infarction in dogs.

In vitro evaluation, cellular uptake and anti-acute myocardial ischemia effect of puerarin PEG-PLGA micelles / 中国中药杂志

PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.

Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury / 中国中药杂志

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of β-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

Non-ST Elevation Myocardial Infarction (NSTEMI) – A Case Study

Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by a high risk of developing arterial and venous thromboembolic complications. In recent years, great insight has been gained into the understanding of the pathogenesis of thrombosis in PV. Diagnosing and managing a case of acute coronary syndrome (ACS) due to non-atherosclerotic causes is a challenge. In this case report, we share our experience in diagnosis, management and revascularization issues in non-ST-elevation myocardial infarction (NSTEMI) in a patient with polycythemia vera background.

Preventive protection of Yingxindan on myocardial ischemia / 中国药理学通报

Aim To observe the preventive protection of Yingxindan on acute myocardial ischemia induced by sublingual injection of pituitrin ( pit) in rats.Methods Sixty rats were randomly divided into saline group , model group, nifedipine 12.6 mg · kg -1 group, and Yingxindan 25.2, 12.6, 6.3 mg · kg -1 groups.The saline group and model group were given the same vol-ume of water.After administration for 7 d, an acute myocardial ischemia model was induced by sublingual intravenous injection of pit 1 U · kg -1 in the rats 1 h after last administration .The changes of the II electro-cardiogram(ECG) ST segment at different time points , as well as the positive rate of myocardial ischemia and arrhythmia were observed .Meanwhile , the levels of serum creatine kinase ( CK ) , creatine kinase isoenzyme ( CK-MB ) , glycogen phosphorylase isoenzyme BB ( GPBB ) , cardiac troponin I ( cTnI ) and cardiac troponin T ( cTnT ) were observed .Re-sults Yingxindan could suppress the changes of ST segment of electrocardiogram in rats with acute myocar-dial ischemia induced by pit and reduce the positive rate of myocardial ischemia and arrhythmia .The con-tents of myocardial injury markers CK , CK-MB, GPBB, cTnI and cTnT in serum significantly de-creased, and the corresponding relationship existed . The greater the dose of Yingxindan , the smaller the content of myocardial injuried markers in serum .Con-clusion Yingxindan has significant preventive protec-tion effect on acute myocardial ischemia by pit .

Role of JAK2/STAT3 signaling pathway in ginsenoside Re pretreatment in prevention of isoproterenol-induced acute myocardial ischemia / 中国药理学通报

Aim To observe the protective effect of ginsenoside Re pretreatment on rats with isoproterenol-induced acute myocardial ischemia via JAK 2/STAT3 signaling pathway .Methods SD rat model with acute myocardial ischemia was established using isoprotere-nol.Seventy-five rats were randomly divided into five groups: control group, model group , puerarin group (PUE), high dose group (Re-H, 20 mg· kg -1) and Re low-dose group ( Re-L, 10 mg kg -1 ) .The blood flow on the heart surface of rats in each group was ob-served by moor laser blood flow imaging system .The levels of CK , LDH, SOD, MDA and GSH in myocar-dium were measured by ELISA .The expressions of Bax and Bcl-2 proteins were detected by immunohistochem-istry.The expressions of JAK , p-JAK, STAT3 and p-STAT3 proteins were detected by Western blot .Re-sults Compared with the control group , the mean blood flow on the heart surface of rats in the model group significantly decreased , the levels of CK , LDH and MDA in the myocardium increased , the levels of GSH and SOD decreased , the ratio of Bcl-2/Bax de-creased ( P <0.05 ) , and the expression of JAK 2/STAT3 pathway related proteins was enhanced ( P <0.05 ) . The mean blood flow on the heart surface markedly increased , the levels of CK , LDH and MDA decreased , the level of GSH-Px increased , the ratio of Bcl-2/Bax increased, and the expression of JAK2/STAT3 pathway proteins evidently increased in the Re-H group compared with those of the model group ( P<0.05 ) .Conclusion Ginsenoside Re pretreatment has a good protective effect on the myocardium in rats with acute myocardial ischemia , which may be related to the activation of JAK2/STAT3 signaling pathway .

Effect of Electroacupuncture on Hippocampal IL-6, IL-1 β, TNF-α and Norepinephrine Levels in Acute Myocardial Ischemia Rats / 针刺研究

OBJECTIVE: We have repeatedly demonstrated that electroacupuncture (EA) stimulation of "Shenmen" (HT 7)- "Tongli" (HT 5) segment of the Heart Meridian can improve acute myocardial ischemia (AMI). This study aimed at observing the effect of EA on contents of hippocampal norepinephrine (NE), and interleukin 6 (IL-6), IL-1 β and tumor necrosis factor- α (TNF-α) in AMI rats, so as to explore its underlying mechanism. METHODS: SD rats were randomly divided into 3 groups: sham operation (sham), model and EA(n=6 rats in each). The anterior descending branch (ADB) of the left coronary artery was occluded to make an AMI model. For rats of the sham group, a surgical suture was simply threaded beneath the ADB without ligation. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Shenmen" (HT 7)- "Tongli" (HT 5) and the middle-point between HT 7 and HT 5 for 30 min, once daily for 3 days. Electrocardiogram (ECG) of the neck-thoracic lead was recorded by using PowerLab 16. The contents of serum creatine kinase (CK), hippocampal IL-6, IL-1 β and TNF-α were assayed by ELISA. The concentration of NE in hippocampal CA 1 area was detected by microdialysis combined with electrochemical detector. RESULTS: Compared with the sham group, the ECG-ST height, serum CK, hippocampal NE, IL-6, IL-1 β and TNF-α contents of the CA 1 region were significantly increased in the model group (P<0.001). Whereas, after EA intervention, the serum CK, hippocampal NE, IL-6, IL-1 β and TNF-α contents were obviously down-regulated relevant to the model group (P<0.05, P<0.001), and the IL-6, IL-1 β and TNF-α contents were positively correlated with the NE level (P<0.001, P<0.01). CONCLUSION: EA stimulation of the Heart Meridian may improve ischemic myocardial injury in AMI rats, probably by reducing the proinflammatory factors and hippocampal NE.

Effect of Electroacupuncture at Different Acupoints on Expression of NGF and TrkA in Cerebral Cortex in Rats with Myocardial Ischemia / 针刺研究

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) of "Shenmen" (HT 7, Yuan point of the Heart Meridian), "Zhizheng" (SI 7, Luo point of the Small Intestine Meridian) and "Xinshu" (BL15, Back-shu point) on the expression of nerve growth factor (NGF) and its receptor, tyrosine kinase A (TrkA) in the cerebral cortex of myocardial ischemia (MI) rats. METHODS: A total of 70 male SD rats were randomized into sham operation (sham, n=10), model, HT 7, SI 7, and BL15 groups (n=15 in each of the latter 4 groups). The MI model was established by ligation of the anterior descending branch of the left coronary artery. EA (1 mA, 2 Hz) was respectively applied to HT 7, SI 7 and BL15 for 15 min, once per day for 1 week. Immunohistochemistry and real-time fluorescent quantitative PCR were used to detect the expression of NGF and TrkA proteins and genes in the cerebral cortex. RESULTS: Compared with the sham group, no significant changes were found in the number of NGF immune-reaction (IR)-positive and TrkA IR-positive cells, and the expression levels of NGF mRNA and TrkA mRNA in the model group (P>0.05). After EA intervention, the number of NGF and TrkA IR-positive cells and the expression of NGF mRNA and TrkA mRNA in each of the 3 EA groups were significantly increased relevant to the model group (P<0.01, P<0.05). The effect of EA at BL 15 was significantly superior to that of EA at HT 7 and SI 7 in increasing the number of NGF and TrkA positive cells and up-regulating the expression of their mRNAs (P<0.01, P<0.05). CONCLUSION: EA at HT 7, SI 7 and BL 15 can increase the levels of expression of NGF and TrkA proteins and mRNAs in the cerebral cortex of subacute MI rats and the effects of EA-BL 15 are obviously superior to those of EA-HT 7 and EA-SI 7, suggesting a relative specificity of the effect of EA at different acupoints.

Expression of visfatin and microRNAs in myocardium of acute myocardial ischemia in rats / 中国糖尿病杂志

Objective To study the expression of visfatin and related mRNAs in myocardium of acute myocardial ischemia in rats,and to explore the role of both in acute myocardial ischemia model and to propose new ideas for clinical cardiovascular diseases.Methods Wistar rats (n=20) were randomly divided into sham operation control group and acute myocardial ischemia groups.Left anterior descending (LAD) of coronary artery was ligated to establish the model of acute myocardial ischemia.The total myocardium proteins were collected 12 h after operation.Western blot was used to observe the expression changes of visfatin in myocardium.The expressions of miR-124 and miR-327 in myocardium were detected by real-time PCR.Results The levels of serum CK and LDH in the model group of myocardial ischemia rats were elevated [(46.20±7.12) vs (72.19±9.38)kU/L;(2542.23±173.54) vs (6428.76±237.81)U/L,P＜0.05)].The visfatin expression levels in the rats of acute myocardial ischemia groups were higher than those in controls [(0.804±0.042) vs (1.046±0.031),P＜0.05].MiR-124 was up regulated and miR-327 was down regulated in acute ischemia myocardium.Cndusion The up-regulation of miR-124,the down-regulation of miR-327 and the increase of visfatin expression may be related to acute myocardial ischemia.The changes of visfatin expression may be regulated by miR-124 and miR-327 posttranscriptional levels.

Preparation of Puerarin-loaded PEG-PE Nano-micelles and Its Tissue Distribution in Acute Myocardial Ischemia Model Mice / 中国药学杂志

OBJECTIVE: To prepare puerarin-loaded PEG-PE nano-micelles and explore its tissue distribution in acute myocardial ischemia model mice. METHODS: Puerarin-loaded PEG-PE nano-micelles were prepared by thin-film hydration method. Sixty KM mice were randomly divided into two groups (30 in each group). Both were given puerarin-loaded PEG-PE nano-micelles at a dose of 20 mgkg-1. After 5 min of medication, the mice in one group were treated with ligation of coronary artery to establish acute myocardial ischemia, and the other one group was taken as the control. The animals were executed at 30, 60, 90, 120, 150 and 180 min, then the heart, liver, spleen, lung, and kidney were extracted. The content of puerarin in the organ tissue was determined by HPLC. RESULTS: The drug loading and drug encapsulation of puerarin-loaded PEG-PE nano-micelles were (5.8±1.3)% and (78.6±5.7)%, respectively, and the diameters and Zeta potential were 25 nm and -3 mV, respectively. The AUCs of tissue distribution of puerarin-loaded PEG-PE nano-micelles in the control group were in the sequence of liver>kidney>heart >spleen>lung>brain. While the AUCs of tissue distribution of PEGylated puerarin in acute myocardial ischemia model mice were in the sequence of liver≈heart>kidney>lung>spleen>brain. The AUCheart of puerarin-loaded PEG-PE nano-micelles in acute myocardial ischemia model mice was 1.9 times of that of the control mice (P<0.05). CONCLUSION: Puerarin-loaded PEG-PE nano-micelles show excellent drug loading capabilities. It has good heart-targeting property in early myocardial infarction area and can accumulate in the ischemic myocardium. This study provides important information for further development of prepamiceion.

Effect of umbilical cord mesenchymal stem cells on VEGF and MCP-1 of acute myocardial ischemia-reperfusion injury in rats / 国际生物医学工程杂志

Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.

Effects of electroacupuncture preconditioning on expression of aquaporin-1 and activity of protein kinase C in myocardium of rats with acute myocardial ischemia-reperfusion injury / 中国针灸

<p><b>OBJECTIVE</b>To explore the partial action mechanism and the myocardial protective effect differences between electroacupuncture (EA) preconditioning at "Neiguan"(PC 6) and "Taiyuan"(LU 9) in rats with acute myocardial ischemia-reperfusion injury.</p><p><b>METHODS</b>Ninety-six Wistar rats were randomly assigned into a sham-operation group, a model group, a Neiguan group and a Taiyuan group, 24 rats in each one. The rats in the Neiguan group and Taiyuan group were treated with EA (2 Hz in frequency, 1 mA in intensity) at "Neiguan" (PC 6) and "Taiyuan" (LU 9) respectively, 20 min per treatment, once a day for consecutive 7 days. The rats in the sham-operation group and model group were treated with immobilization for the same time, and no EA was given. The model of myocardial ischemia-reperfusion injury was established in the model group, Neiguan group and Taiyuan group 24 h after the end of EA, while the rats in the sham-operation group were treated with sham operation (no ligation was made during surgery). The myocardial ischemic size, infarction size, activity of protein kinase C (PKC) and expression of aquaporin1 (AQP1) in each group were detected.</p><p><b>RESULTS</b>Compared with sham-operation group, the myocardial ischemic size, infarction size, AQP1 expression and PKC activity in the model group were significantly increased (all<0.01); compared with the model group and Taiyuan group, the myocardial ischemic size, infarction size, PKC activity and AQP1 expression were significantly decreased in the Neiguan group (<0.01,<0.05). By Pearson correlation analysis, the changes of AQP1 expression were positively correlated with those of PKC activity after EA preconditioning.</p><p><b>CONCLUSIONS</b>EA preconditioning at "Neiguan" (PC 6) could significantly decrease myocardial AQP1 expression and PKC activity in rats with acute myocardial ischemia-reperfusion injuing, but the effect of EA preconditioning at "Taiyuan"(LU 9) is not obvious; its protective effect is likely to be achieved by inhibiting PKC activity and AQP1 expression.</p>

1H NMR-based metabolomics study of intervention effects ofleonurine on acute myocardial ischemia in rats / 中国药理学通报

Aim To investigate metabolomic profiles of acute myocardial ischemia (AMI) in rat plasma and explore the intervention effects and its mechanism of leonurine using a metabolomics approach based on nuclear magnetic resonance (NMR).Methods The plasma metabolomic characteristics in rats of sham group,AMI model group,and leonurine-treated group were detected by 1H NMR,and the different metabolites between AMI group and sham group or leonurine-treated group were analyzed by pattern recognition and multivariate data analysis.Results Orthogonal partial least squares discriminant analysis (OPLS-DA) demonstrated that six metabolites related to AMI were screened out,including alanine,lysine,glycine,creatine,N-acetyl glycoprotein,and O-acetyl glycoprotein and all their levels were elevated in AMI group compared to sham group.Treatment of leonurine decreased the levels of alanine,lysine,and glycine,and increased the levels of choline,phosphocholine,and scyllo-inositol compared with the model group.Conclusions Leonurine can improve amino acid metabolism disorder under AMI conditions and enhance the function of choline and inositol pathway,which may explain its cardioprotective effect.The developed metabolomics approach in this study is a powerful tool for the investigation of the cardioprotective effect of leonurine and provide a new insight to understand its pharmacological mechanism.

Effects of Ang II perfusion on transmural heterogeneous of Cx43 in acute myocardial ischemia reperfusion

Objective: To observe the effects of angiotensin II(Ang II) perfusion on transmural heterogeneity of Cx43 expression in the rabbit model with acute myocardial ischemia reperfusion (MIR), and investigate the role of rennin-angiotensin system in malignant ventricular arrhythmia induced by MIR. Methods: Twenty rabbits were randomly divided into MIR group (n = 10) and Ang II group (n = 10). MIR model was produced with traditional ligation and opening of the anterior descending coronary artery in all animal. The hearts in vitro in the MIR group and the Ang II group were perfused with simply improved Tyrode's solution and containing Ang II Tyrode's solution respectively. 90% monophasic action potential repolarization duration, transmural dispersion of repolarization, Cx43 protein (Cx43-pro) and mRNA (Cx43-Cq) expression in subepicardial, midmyocardial and subendocardial myocardium were measured in both groups. The greatest differences of Cx43-pro and Cx43-Cq among three myocardial layers were calculated and shown with ΔCx43-pro and ΔCx43-Cq respectively. Results: After Ang II perfusion, 90% monophasic action potential repolarization duration among three myocardial layer were significantly prolonged (P < 0.05 and P < 0.01), and transmural dispersion of repolarization also significantly increased compared with the MIR group (P < 0.05). Compare with the MIR group, three myocardial Cx43-pro and Cx43-Cq expression in the Ang II group were significantly decreased (P < 0.05 and P < 0.01), but ΔCx43-pro and ΔCx43-Cq were significant increased. Conclusions: Renin-angiotensin system increases transmural heterogeneity of Cx43 expression in the rabbit model with MIR by Ang II, and enlarge transmural dispersion of repolarization among three myocardial layers of left ventricular which induces malignant ventricular arrhythmia.