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...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.展开更多
Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,SXJ)on myocardial ischemia and reperfusion(I/R)injury.Methods:Mouse myocardial I/R injury model was created by 30-min coro...Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,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-3β(GSK3β),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/GSK3βand nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3βand GATA4 signaling pathways.展开更多
目的综合运用多维联用技术,建立日本救心丹HPLC-UV/ELSD和HPLC-UV/MS3指纹图谱研究方法,初步阐明其化学物质基础。方法A ltim a C18色谱柱(250 mm×4.6 mm ID,5μm);流动相为乙腈-0.2%甲酸水体系;梯度洗脱;流速1.0 mL.m in-1;检测波...目的综合运用多维联用技术,建立日本救心丹HPLC-UV/ELSD和HPLC-UV/MS3指纹图谱研究方法,初步阐明其化学物质基础。方法A ltim a C18色谱柱(250 mm×4.6 mm ID,5μm);流动相为乙腈-0.2%甲酸水体系;梯度洗脱;流速1.0 mL.m in-1;检测波长286 nm。ELSD条件为漂移管温度110℃,N2流速2.5 L.m in-1。采用电喷雾离子阱质谱分析,正、负离子三级扫描。结果建立了日本救心丹HPLC-UV/ELSD多维指纹图谱,同时通过MS定性鉴别出21种成分,并推测可能存在去氧苷胆酸及其异构体。方法稳定且重现性好。结论该研究为分析汉方中药复杂体系提供了一种有效、可靠的模式。展开更多
基金Supported by the National Natural Science Foundation of Guangdong(No.2020A1515010777)。
文摘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.
基金Supported by the National Natural Science Foundation of China(No.81473471 and No.81603429)Foundation of Guangdong Hospital of Chinese Medicine(No.YK2013B2N11,No.YN2014ZH01,No.YN2014ZHR203,and No.YN2016QJ19)。
文摘Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,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-3β(GSK3β),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/GSK3βand nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3βand GATA4 signaling pathways.
