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1.
Chin J Integr Med ; 29(2): 108-118, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36327050

ABSTRACT

OBJECTIVE: To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent. METHODS: VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models. RESULTS: SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG. CONCLUSION: SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.


Subject(s)
Arrhythmias, Cardiac , Calcium , Animals , Rabbits , Mice , Computer Simulation , Electrocardiography
2.
Chin J Integr Med ; 26(8): 583-590, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32524394

ABSTRACT

OBJECTIVE: To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury. METHODS: Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3ß (GSK3ß), and protein expression of GATA4 in nucleus were detected with Western blot assay. RESULTS: The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4% ±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3ß and nuclear expression of GATA4. CONCLUSION: SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3ß and GATA4 signaling pathways.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Myocardial Reperfusion Injury/drug therapy , Animals , Cell Line , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Myocytes, Cardiac , Rats, Sprague-Dawley
3.
Chin J Integr Med ; 24(8): 613-620, 2018 Aug.
Article in English | MEDLINE | ID: mdl-27048409

ABSTRACT

OBJECTIVE: To observe the in vivo effect of Danlou Tablet (, DLT) on myocardial ischemia and reperfusion (I/R) injury. METHODS: DLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group (n=6), I/R group (n=8), IPC group (ischemia preconditioning, n=6) and DLT group (I/R with DLT pretreatment for 3 days, 750 mg•kg-1•day-1, n=8). The effects of DLT were characterized in infarction size (IS) compared with risk region (RR) and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo. Furthermore, the dose-dependent effect of DLT on I/R injury was evaluated by double staining method. Five different concentrations of DLT (0.625, 1.25, 2.5, 5 and 10 g•kg-1•day-1) were chosen in this study, and dose-response curve of DLT was obtained on these data. RESULTS: The ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group (P<0.05 or P<0.01), the ratio of IS to RR was also reduced in the DLT and IPC groups (P<0.01), while there were no differences in RR among the four groups (P>0.05). Experiments showed incidence of arrhythmias was reduced in the DLT group (P<0.01). Furthermore, DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g•kg-1•day-1. CONCLUSIONS: Our research concluded that DLT was effective in reducing I/R injury in mice, and provided experimental supports for the clinical use of DLT.


Subject(s)
Cardiotonic Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/pathology , Arrhythmias, Cardiac/physiopathology , Body Temperature/drug effects , Cardiotonic Agents/pharmacology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Heart Rate/drug effects , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Male , Mice, Inbred C57BL , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Risk Factors , Tablets
4.
Chin J Integr Med ; 23(9): 643-647, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28861886

ABSTRACT

Ventricular remodeling (VR) can be induced by myocardial injury, leading to progressive cardiac dysfunction and heart failure, and is associated with high morbidity and mortality. Despite being studied for more than 3 decades, current therapeutic strategies still remain unsatisfactory in effificacy, expensive, and with side effects and drug resistances. Chinese medicine (CM) has been used to treat heart diseases for thousands of years. This article reviews the published studies on the mechanisms and therapeutic applications of CM in VR. The major aspects include: mechanistic studies of VR, molecular biology and myocardial functional studies of CM therapies on VR, and mechanism of CM therapies on VR.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Precision Medicine , Ventricular Remodeling/drug effects , Humans , Signal Transduction/drug effects
5.
Chin J Integr Med ; 23(1): 40-47, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27787719

ABSTRACT

OBJECTIVE: To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury. METHODS: Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes. RESULTS: There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively). CONCLUSION: Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.


Subject(s)
MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocardial Reperfusion Injury/drug therapy , Plant Extracts/therapeutic use , Animals , Blotting, Western , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Flavonoids/pharmacology , Heart Ventricles/drug effects , Heart Ventricles/pathology , MAP Kinase Signaling System/drug effects , Male , Mice, Inbred C57BL , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/pathology , Organ Size/drug effects , Phosphorylation/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protein Kinase Inhibitors/pharmacology , Staining and Labeling
6.
Chin J Integr Med ; 21(9): 662-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26142341

ABSTRACT

BACKGROUND: It has been shown that administration of statins reduced the risk of peri-procedural myocardial damage. However, it remains unclear whether Chinese medicine Danlou Tablet (), similar to statins, may protect patients undergoing percutaneous coronary intervention (PCI) from peri-procedural myocardial damage. OBJECTIVE: To demonstrate the hypothesis whether treatment with Danlou Tablet would improve clinical outcome in patients undergoing selective PCI with non-ST elevation acute coronary syndrome (NSTE-ACS) in China. METHODS: Approximately 220 patients with unstable angina or non-ST-segment elevation myocardial infarction undergoing PCI will be enrolled and randomized to Danlou Tablet treatment (4.5 g/day for 2 days before intervention, with a further 4.5 g/day for 90 days thereafter) or placebo. All patients will not receive Danlou Tablet before procedure. The primary end point is to evaluate the incidence of cardiac death, myocardial infarction or unplanned re-hospitalization and revascularization after 30 days in patients undergoing selective PCI treated with Danlou Tablet compared with placebo. Secondary endpoints include the incidence of peri-procedural myocardial injury, 3-month clinical outcomes, the quality of life and Chinese medicine syndromes assessment. CONCLUSION: This study protocol will provide important evidence of Danlou Tablet treatment on the peri-procedural myocardial injury in patients with NSTE-ACS undergoing selective PCI, which may support a strategy of routine Danlou Tablet therapy to improve the clinical outcomes.


Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/drug therapy , Drugs, Chinese Herbal/therapeutic use , Electrocardiography , Myocardium/pathology , Percutaneous Coronary Intervention , Endpoint Determination , Humans , Sample Size , Ultrasonography
7.
Clin Exp Pharmacol Physiol ; 37(3): 296-302, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19719751

ABSTRACT

1. Insulin-like growth factor (IGF)-I plays an important role in the pathogenesis of heart disease and has been shown to strongly induce the proliferation of cardiac fibroblasts (CFs). It remains unknown whether 14-3-3 proteins, which are associated the regulation of signal transduction, affect IGF-I-induced CF proliferation. 2. In the present study, we investigated the effects of 14-3-3 proteins on CF proliferation in response to IGF-I. Proliferation of CFs was determined by cell counting and a bromodeoxyuridine incorporation assay. Phosphorylation of signalling molecules was evaluated by western blottling. Activity of nuclear factor of activated T cells (NFAT) was examined using a dual luciferase reporter gene assay and immunofluorescence. 3. It was found that adenovirus-mediated transfection of YFP-R18 peptide (AdR18), a known inhibitor of 14-3-3, significantly enhanced IGF-I-induced CF proliferation. This potentiation arose from an increase in phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and AKT (protein kinase B), inactivation of glycogen synthesis kinase (GSK) 3beta and increased NFAT activity. 4. Collectively, the results of the present study suggest that 14-3-3 proteins inhibit IGF-I-induced CF proliferation via a PI3-K-dependent NFAT signalling pathway. This finding may contribute to our understanding of the function of 14-3-3 proteins in the heart.


Subject(s)
14-3-3 Proteins/metabolism , Cell Proliferation , Fibroblasts/cytology , Insulin-Like Growth Factor I/pharmacology , Myocardium/cytology , Phosphatidylinositol 3-Kinase/physiology , 14-3-3 Proteins/antagonists & inhibitors , Animals , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Fibroblasts/enzymology , Fibroblasts/metabolism , Humans , Mice , Mice, Inbred C57BL , Myocardium/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology
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