Objective:To study the effect of Shexiang Tongxin Dropping Pill combined with thrombus aspiration on improving myocardial perfusion after PCI in patients with STEMI.Methods:A total of 104 patients with STEMI who recei...Objective:To study the effect of Shexiang Tongxin Dropping Pill combined with thrombus aspiration on improving myocardial perfusion after PCI in patients with STEMI.Methods:A total of 104 patients with STEMI who received emergency PCI combined with thrombus aspiration in our hospital between May 2013 and October 2015 were selected as the research subjects and randomly divided into two groups: observation group received perioperative antiplatelet combined with Shexiang Tongxin Dropping Pill therapy, and the control group received perioperative antiplatelet therapy alone. Before treatment and 3 days after treatment, serum myocardial injury indexes, endothelial injury indexes and RAS system indexes were determined;4 weeks after treatment, serum ventricular remodeling indexes were determined. Results:3 d after treatment, serum CK, CK-MB, cTnI, cTnT, ET-1, vWF, PRA, AngII and ALD levels of both groups were significantly lower than those before treatment while NO level was significantly higher than that before treatment;serum CK, CK-MB, cTnI, cTnT, ET-1, vWF, PRA, AngII and ALD levels of observation group 3 d after treatment were significantly lower than those of control group while NO level was significantly higher than that of control group;4 weeks after treatment, serum PICP, ICTP, PIIINP, HSP47 and GDF-15 levels of observation group were significantly lower than those of control group.Conclusion: Shexiang Tongxin Dropping Pill application during perioperative period of PCI combined with thrombus aspiration can reduce myocardial cell damage and endothelial function injury as well as inhibit RAS system activation and ventricular remodeling.展开更多
Objective:To study the effect of Shexiang Tongxin Dropping Pill(STDP)on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction(CMD).Methods:According to a random number table,6 of 36 S...Objective:To study the effect of Shexiang Tongxin Dropping Pill(STDP)on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction(CMD).Methods:According to a random number table,6 of 36 SPF male C57BL/6 mice were randomly selected as the control group,and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model.Mice successfully copied the diabetes model were randomly divided into the model group,STDP low-dose group[15 mg/(kg·d)],medium-dose group[30 mg/(kg·d)],high-dose group[60 mg/(kg·d)],and nicorandil group[15 mg/(kg·d)],6 in each group.The drug was given by continuous gavage for 12 weeks.The cardiac function of mice in each group was detected at the end of the experiment,and coronary flow reserve(CFR)was detected by chest Doppler technique.Pathological changes of myocardium were observed by hematoxylin-eosin staining,collagen fiber deposition was detected by masson staining,the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining,and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining.The expression of the vascular endothlial growth factor(VEGF)/endothelial nitric oxide synthase(eNOS)signaling pathway-related proteins in myocardial tissue was detected by Western blot.Results:Compared with the model group,medium-and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening(P<0.01),obviously repaired the disordered cardiac muscle structure,reduced myocardial fibrosis,reduced myocardial cell area,increased capillary density,and increased CFR level(all P<0.01).Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2,phosphoinositide 3-kinase,protein kinase B,and eNOS(P<0.05 or P<0.01).Conclusion:STDP has a definite therapeutic effect on diabetic CMD,and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.展开更多
Objective:To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills(STDP) on heart failure(HF).Methods:Isoproterenol(ISO)-induced HF rat model and angiotensin Ⅱ(Ang Ⅱ)-induced neon...Objective:To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills(STDP) on heart failure(HF).Methods:Isoproterenol(ISO)-induced HF rat model and angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat cardiac fibroblast(CFs) model were used in the present study.HF rats were treated with and without STDP(3 g/kg).RNA-seq was performed to identify differentially expressed genes(DEGs).Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson’s stainings were taken to assess cardiac fibrosis.The levels of collagen Ⅰ(Col Ⅰ) and collagen Ⅲ(Col Ⅲ) were detected by immunohistochemical staining.CCK8 kit and transwell assay were implemented to test the CFs’ proliferative and migratory activity,respectively.The protein expressions of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),MMP-9,Col I,and Col Ⅲ were detected by Western blotting.Results:The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways,such as the extracellular matrix(ECM)-receptor interaction,cell cycle,and B cell receptor interaction.Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function,inhibiting myocardial fibrosis,and reversing increases in Col Ⅰ and Col Ⅱ expression levels in the hearts of HF rats.Moreover,STDP(6,9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang Ⅱin vitro(P<0.05).The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP,also the synthesis of MMP-2 and MMR-9,as well as ECM components Col Ⅰ,Col Ⅲ,and α-SMA were decreased in Ang Ⅱ-induced neonatal rats’ CFs.Conclusions:STDP had anti-fibrotic effects in HF,which might be caused by the modulation of ECM-receptor interaction pathways.Through the management of cardiac fibrosis,STOP may be a compelling candidate for improving prognosis of HF.展开更多
目的 探讨脂肪因子代谢对冠状动脉微血管功能障碍(MVD)的影响及麝香通心滴丸(STDP)的临床应用价值。方法 纳入2018年9月至2019年12月上海交通大学医学院附属新华医院心内科收治的41例冠心病患者,分为非MVD组(20例)和MVD组(21例);29例MV...目的 探讨脂肪因子代谢对冠状动脉微血管功能障碍(MVD)的影响及麝香通心滴丸(STDP)的临床应用价值。方法 纳入2018年9月至2019年12月上海交通大学医学院附属新华医院心内科收治的41例冠心病患者,分为非MVD组(20例)和MVD组(21例);29例MVD患者随机分为基础治疗组(14例)和STDP组(15例),分别进行为期3个月的基础治疗和基础治疗加STDP治疗;分析各组患者主诉、血生物化学指标、血浆炎症因子及脂肪因子水平的变化。采用12~14周龄雄性C57BL/6小鼠制备心肌缺血再灌注(IR)模型,分为假手术组、IR组(生理盐水灌胃)和IR+STDP组(STDP灌胃),每组5只,采用ELISA测定血浆炎症因子水平,通过硫黄素-S荧光密度法测定心脏组织微血管阻塞情况,采用蛋白质组学分析探寻IR组与IR+STDP组间差异表达蛋白质并通过蛋白质印迹法进行验证。结果 与非MVD组比较,MVD组血浆瘦素水平增高[(9.89±2.42)μg/L vs (4.76±1.02)μg/L,P<0.01],脂联素水平下降[(5.02±1.30)pg/mL vs (7.19±1.76)pg/mL,P<0.05],抵抗素水平升高[(9.20±2.03)μg/L vs (5.70±1.32)μg/L,P<0.05]。Pearson相关分析显示血浆瘦素水平与微循环阻力呈正相关(r=0.82,P<0.01)。ROC曲线分析结果显示,根据血浆瘦素水平判断MVD的AUC值为0.855,最佳临界值为>9.395 μg/L,灵敏度为0.714,特异度为0.867。MVD患者治疗3个月后,相较于基础治疗组,STDP组主诉胸闷、胸痛症状改善率较高[73.3%(11/15) vs 21.4% (3/14)],血浆瘦素、IL-6、TNF-α水平均降低[(11.36±0.54)μg/L vs (12.12±0.85)μg/L、(3.96±1.76)pg/mL vs (8.65±1.29)pg/mL、(24.82±3.07)ng/mL vs (32.45±3.32)ng/mL,均P<0.05]。在动物实验中,与IR组相比,IR+STDP组小鼠IR术后无回流面积减少45%(P<0.01)、低回流及无回流面积减少23%(P<0.05),血浆IL-6、TNF-α水平均下降[(378.25±19.66)pg/mL vs (457.32±32.01)pg/mL、(289.71±47.62)pg/mL vs (371.28±41.05)pg/mL,均P<0.05]。蛋白质组学分析结果显示,IR+STDP组小鼠心脏组织中血管性血友病因子(vWF)、细胞间黏附分子-1(ICAM-1)蛋白质表达水平低于IR组,蛋白质印迹法验证结果亦提示IR+STDP组vWF及ICAM-1蛋白质表达较IR组下调(均P<0.01)。结论 MVD患者存在脂肪因子代谢异常,血浆瘦素水平较高。STDP治疗可改善MVD患者的临床症状,降低血浆瘦素水平和炎症指标,机制可能与其抗血小板、抗炎作用有关。展开更多
Objective: To observe the immediate effect and safety of Shexiang Tongxin dropping pills(麝香通心滴丸, STDP) on patients with coronary slow flow(CSF), and furthermore, to explore new evidence for the use of Chinese me...Objective: To observe the immediate effect and safety of Shexiang Tongxin dropping pills(麝香通心滴丸, STDP) on patients with coronary slow flow(CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. Methods: Coronary angiography(CAG) with corrected thrombolysis in myocardial infarction(TIMI) frame count(CTFC) was applied(collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary?ow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood ?ow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. Results: There was a signi?cant difference in CTFC between groups(P<0.05). The average CTFC values of the vessels with slow blood ?ow in CSF patients were, respectively, 49.98±10.01 and 40.42±11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values(frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00±13.32 and 41.80±15.38, 59.00±4.69 and 50.00±9.04, and 51.90±8.40 and40.09±10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow ?ow before treatment were signi?cantly decreased after treatment(P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP(all P>0.05). Conclusions: The immediate effect of STDP in treating CSF patients was apparent. This medication could signi?cantly improve coronary ?ow without affecting blood pressure or heart rate. Our ?ndings support the potential of Chinese medicine to treat ischemic chest pain.展开更多
Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and level...Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following Na2S2O4-induced hypoxia using Hoechst staining, annexin V/propidium iodide(PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis. Results: STP pretreatment signi?cantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by Na2S2O4 treatment(P<0.05). In addition, STP pretreatment attenuated Na2S2O4-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax,and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells(P<0.05). Conclusions: STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis.These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.展开更多
OBJECTIVE:To investigate the protective effects of Shexiang Tongxin dropping pill(麝香通心滴丸,STDP)in a rat model of coronary microcirculatory dysfunction(CMD).METHODS:Sprague-Dawley rats were allocated randomly into...OBJECTIVE:To investigate the protective effects of Shexiang Tongxin dropping pill(麝香通心滴丸,STDP)in a rat model of coronary microcirculatory dysfunction(CMD).METHODS:Sprague-Dawley rats were allocated randomly into four groups:sham,CMD model,STDP,and nicorandil.After 4 weeks of treatment,CMD was induced by injection of sodium laurate(0.2 m L,2 g/L)into the left ventricle while obstructing the ascending aorta.Rats in the sham group underwent an identical surgical procedure but were administered physiological(0.9%)saline(0.2 m L).Twenty-four hours after surgery,blood samples were collected for biochemical analyses and enzyme-linked immunosorbent assays.Heart tissues were removed for histopathology staining;apoptosis and inflammatory cytokines were examined by Western blotting.RESULTS:The STDP group had a lower level of creatine kinase-myocardial band,lactate dehydrogenase,and cardiac troponin-I than that in the CMD model group.Infiltration of inflammatory cells,myocardial ischaemia,and microthrombosis were relieved in the STDP group compared with CMD model group.Levels of endothelin-1,nuclear factor-kappa B,tumour necrosis factor-α,interleukin-6,interleukin-1β,malondialdehyde,B-cell lymphoma(Bcl)-2-associated X protein,and caspase-3 were lower,and levels of nitric oxide,Bcl-2,and superoxide dismutase were higher,in the STDP group in comparison with the CMD model group.CONCLUSION:STDP pretreatment improved the CMD induced by sodium laurate via anti-inflammatory,anti-apoptosis,and anti-oxidant mechanisms.展开更多
Objective To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STDP)following sodium laurate-induced coronary microembolization(CME)in rats.Methods Forty rats were divided into 4 groups...Objective To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STDP)following sodium laurate-induced coronary microembolization(CME)in rats.Methods Forty rats were divided into 4 groups:the control(sham)group,CME group,low-dose STDP pretreatment group(20 mg·kg^(−1)·d^(−1)),and high-dose STDP pretreatment group(40 mg·kg^(−1)·d^(−1)).The rats were intragastric administrated with STDP 2 weeks before operation.Moreover,the histopathological alterations were observed using optical microscopy and transmission electron microscopy.Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay.Mitochondrial functions including the mitochondrial permeability transition pore(mPTP)mtDNA copy number were determined and proteins of AKT/GSK3βwere analyzed by Western blot.Results The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers(superoxide dismutase and catalase,P<0.01 for all).In contrast,the rats in the low-and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi(P<0.05);moreover,STDP restored the antioxidant-related protein activities and mitochondrial function,inhibited mPTP opening,decreased AKT-Ser473 phosphorylation,and increased GSK3β-Ser9 phosphorylation(P<0.05 or P<0.01).Conclusion STDP may be useful for treatment of CME,possibly via regulation of mPTP opening and AKT/GSK3βphosphorylation.展开更多
目的:基于网络药理学方法探究参蛭通心胶囊核心药对人参-水蛭治疗扩张型心肌病(dilated cardiomyopathy,DCM)的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and an...目的:基于网络药理学方法探究参蛭通心胶囊核心药对人参-水蛭治疗扩张型心肌病(dilated cardiomyopathy,DCM)的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、BATMAN-TCM数据库获取人参-水蛭药对的活性成分及潜在靶点并导入UniProt数据库对所得基因进行标准化处理;运用人类基因数据库(the human gene database,GeneCards)获取DCM已知靶点;通过绘制韦恩图得到药物与疾病的交集靶点,将药物活性成分及药物-疾病共同靶点等数据导入Cytoscape 3.7.2软件,构建药物-成分-疾病-靶点网络;运用STRING数据库构建蛋白-蛋白互作网络(protein-protein interactions,PPI)并筛选出核心靶点;将核心靶基因导入基因功能注释数据库(the database for annotation visualization and integrated discovery,DAVID)平台对所得交集靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,同时利用OmicShare进行数据的可视化分析。结果:经筛选共获得人参-水蛭药对有效成分35个,药物-疾病交集靶点184个,涉及的核心靶点主要有胰岛素、白蛋白、肿瘤坏死因子、内皮一氧化氮合成酶、过氧化物酶体增殖物激活受体、白细胞介素1β等。人参-水蛭的有效成分通过对细胞膜、细胞外间隙、电压门控钙通道复合体等部位的作用、一氧化氮生物合成过程的正调控、细胞间信号传递、对凋亡过程的负调控等过程和CAMP信号通路等在内的多个信号通路协同作用治疗DCM。结论:参蛭通心胶囊的核心药对人参-水蛭可以通过参与调控多成分、多靶点、多通路治疗DCM。展开更多
Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is ...Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is a traditional Chinese medicine to treat angina pectoris.STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice.However,whether STDP can affect platelet function remains unknown.Objective:The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention(PCI)for unstable angina.The interaction between the effects of STDP with polymorphisms of CYP2 C19 was also investigated.Design,participants and intervention:This was a single-center,randomized controlled trial in patients undergoing elective PCI for unstable angina.Eligible subjects were randomized to receive STDP(210 mg per day)plus dual antiplatelet therapy(DAPT)with clopidogrel and aspirin or DAPT alone.Main outcome measures:The primary outcome was platelet function,reflected by adenosine diphosphate(ADP)-induced platelet aggregation and platelet microparticles(PMPs).The secondary outcomes were major adverse cardiovascular events(MACEs)including recurrent ischemia or myocardial infarction,repeat PCI and cardiac death;blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme(CK-MB)and high-sensitive troponin I(hs Tn I);and biomarkers for inflammation including intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),monocyte chemoattractant protein-1(MCP-1)and galectin-3.Results:A total of 118 subjects(mean age:[66.8±8.9]years;male:59.8%)were included into analysis:58 in the control group and 60 in the STDP group.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(P>0.05)at 24 h after PCI,lower ICAM-1,VCAM-1,MCP-1 and galectin-3 at 3 months(all P<0.05)but not at 7 days after PCI(P>0.05).At 3 months,the STDP group had lower PMP number([42.9±37.3]vs.[67.8±53.1]counts/μL in the control group,P=0.05).Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers(66.0%±20.8%in STDP group vs.36.0%±28.1%in the control group,P<0.05),but not in intermediate or fast metabolizers.The rate of MACEs during the 3-month follow-up did not differ between the two groups.Conclusion:STDP produced antiplatelet,anti-inflammatory and cardioprotective effects.Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.展开更多
文摘Objective:To study the effect of Shexiang Tongxin Dropping Pill combined with thrombus aspiration on improving myocardial perfusion after PCI in patients with STEMI.Methods:A total of 104 patients with STEMI who received emergency PCI combined with thrombus aspiration in our hospital between May 2013 and October 2015 were selected as the research subjects and randomly divided into two groups: observation group received perioperative antiplatelet combined with Shexiang Tongxin Dropping Pill therapy, and the control group received perioperative antiplatelet therapy alone. Before treatment and 3 days after treatment, serum myocardial injury indexes, endothelial injury indexes and RAS system indexes were determined;4 weeks after treatment, serum ventricular remodeling indexes were determined. Results:3 d after treatment, serum CK, CK-MB, cTnI, cTnT, ET-1, vWF, PRA, AngII and ALD levels of both groups were significantly lower than those before treatment while NO level was significantly higher than that before treatment;serum CK, CK-MB, cTnI, cTnT, ET-1, vWF, PRA, AngII and ALD levels of observation group 3 d after treatment were significantly lower than those of control group while NO level was significantly higher than that of control group;4 weeks after treatment, serum PICP, ICTP, PIIINP, HSP47 and GDF-15 levels of observation group were significantly lower than those of control group.Conclusion: Shexiang Tongxin Dropping Pill application during perioperative period of PCI combined with thrombus aspiration can reduce myocardial cell damage and endothelial function injury as well as inhibit RAS system activation and ventricular remodeling.
基金Supported by the National Natural Science Foundation of China(No.81930113)。
文摘Objective:To study the effect of Shexiang Tongxin Dropping Pill(STDP)on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction(CMD).Methods:According to a random number table,6 of 36 SPF male C57BL/6 mice were randomly selected as the control group,and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model.Mice successfully copied the diabetes model were randomly divided into the model group,STDP low-dose group[15 mg/(kg·d)],medium-dose group[30 mg/(kg·d)],high-dose group[60 mg/(kg·d)],and nicorandil group[15 mg/(kg·d)],6 in each group.The drug was given by continuous gavage for 12 weeks.The cardiac function of mice in each group was detected at the end of the experiment,and coronary flow reserve(CFR)was detected by chest Doppler technique.Pathological changes of myocardium were observed by hematoxylin-eosin staining,collagen fiber deposition was detected by masson staining,the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining,and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining.The expression of the vascular endothlial growth factor(VEGF)/endothelial nitric oxide synthase(eNOS)signaling pathway-related proteins in myocardial tissue was detected by Western blot.Results:Compared with the model group,medium-and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening(P<0.01),obviously repaired the disordered cardiac muscle structure,reduced myocardial fibrosis,reduced myocardial cell area,increased capillary density,and increased CFR level(all P<0.01).Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2,phosphoinositide 3-kinase,protein kinase B,and eNOS(P<0.05 or P<0.01).Conclusion:STDP has a definite therapeutic effect on diabetic CMD,and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.
基金Supported by Foundation of Guangdong Province of Traditional Chinese Medicine(No.20201142)Medical Scientific Research Foundation of Guangdong Province(No.A2020323)。
文摘Objective:To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills(STDP) on heart failure(HF).Methods:Isoproterenol(ISO)-induced HF rat model and angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat cardiac fibroblast(CFs) model were used in the present study.HF rats were treated with and without STDP(3 g/kg).RNA-seq was performed to identify differentially expressed genes(DEGs).Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson’s stainings were taken to assess cardiac fibrosis.The levels of collagen Ⅰ(Col Ⅰ) and collagen Ⅲ(Col Ⅲ) were detected by immunohistochemical staining.CCK8 kit and transwell assay were implemented to test the CFs’ proliferative and migratory activity,respectively.The protein expressions of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),MMP-9,Col I,and Col Ⅲ were detected by Western blotting.Results:The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways,such as the extracellular matrix(ECM)-receptor interaction,cell cycle,and B cell receptor interaction.Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function,inhibiting myocardial fibrosis,and reversing increases in Col Ⅰ and Col Ⅱ expression levels in the hearts of HF rats.Moreover,STDP(6,9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang Ⅱin vitro(P<0.05).The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP,also the synthesis of MMP-2 and MMR-9,as well as ECM components Col Ⅰ,Col Ⅲ,and α-SMA were decreased in Ang Ⅱ-induced neonatal rats’ CFs.Conclusions:STDP had anti-fibrotic effects in HF,which might be caused by the modulation of ECM-receptor interaction pathways.Through the management of cardiac fibrosis,STOP may be a compelling candidate for improving prognosis of HF.
文摘目的 探讨脂肪因子代谢对冠状动脉微血管功能障碍(MVD)的影响及麝香通心滴丸(STDP)的临床应用价值。方法 纳入2018年9月至2019年12月上海交通大学医学院附属新华医院心内科收治的41例冠心病患者,分为非MVD组(20例)和MVD组(21例);29例MVD患者随机分为基础治疗组(14例)和STDP组(15例),分别进行为期3个月的基础治疗和基础治疗加STDP治疗;分析各组患者主诉、血生物化学指标、血浆炎症因子及脂肪因子水平的变化。采用12~14周龄雄性C57BL/6小鼠制备心肌缺血再灌注(IR)模型,分为假手术组、IR组(生理盐水灌胃)和IR+STDP组(STDP灌胃),每组5只,采用ELISA测定血浆炎症因子水平,通过硫黄素-S荧光密度法测定心脏组织微血管阻塞情况,采用蛋白质组学分析探寻IR组与IR+STDP组间差异表达蛋白质并通过蛋白质印迹法进行验证。结果 与非MVD组比较,MVD组血浆瘦素水平增高[(9.89±2.42)μg/L vs (4.76±1.02)μg/L,P<0.01],脂联素水平下降[(5.02±1.30)pg/mL vs (7.19±1.76)pg/mL,P<0.05],抵抗素水平升高[(9.20±2.03)μg/L vs (5.70±1.32)μg/L,P<0.05]。Pearson相关分析显示血浆瘦素水平与微循环阻力呈正相关(r=0.82,P<0.01)。ROC曲线分析结果显示,根据血浆瘦素水平判断MVD的AUC值为0.855,最佳临界值为>9.395 μg/L,灵敏度为0.714,特异度为0.867。MVD患者治疗3个月后,相较于基础治疗组,STDP组主诉胸闷、胸痛症状改善率较高[73.3%(11/15) vs 21.4% (3/14)],血浆瘦素、IL-6、TNF-α水平均降低[(11.36±0.54)μg/L vs (12.12±0.85)μg/L、(3.96±1.76)pg/mL vs (8.65±1.29)pg/mL、(24.82±3.07)ng/mL vs (32.45±3.32)ng/mL,均P<0.05]。在动物实验中,与IR组相比,IR+STDP组小鼠IR术后无回流面积减少45%(P<0.01)、低回流及无回流面积减少23%(P<0.05),血浆IL-6、TNF-α水平均下降[(378.25±19.66)pg/mL vs (457.32±32.01)pg/mL、(289.71±47.62)pg/mL vs (371.28±41.05)pg/mL,均P<0.05]。蛋白质组学分析结果显示,IR+STDP组小鼠心脏组织中血管性血友病因子(vWF)、细胞间黏附分子-1(ICAM-1)蛋白质表达水平低于IR组,蛋白质印迹法验证结果亦提示IR+STDP组vWF及ICAM-1蛋白质表达较IR组下调(均P<0.01)。结论 MVD患者存在脂肪因子代谢异常,血浆瘦素水平较高。STDP治疗可改善MVD患者的临床症状,降低血浆瘦素水平和炎症指标,机制可能与其抗血小板、抗炎作用有关。
基金Supported by the Zhejiang Institute of Integrative Medicine Clinical Special Fund for Pharmacy Research(No.2014LYK009)
文摘Objective: To observe the immediate effect and safety of Shexiang Tongxin dropping pills(麝香通心滴丸, STDP) on patients with coronary slow flow(CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. Methods: Coronary angiography(CAG) with corrected thrombolysis in myocardial infarction(TIMI) frame count(CTFC) was applied(collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary?ow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood ?ow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. Results: There was a signi?cant difference in CTFC between groups(P<0.05). The average CTFC values of the vessels with slow blood ?ow in CSF patients were, respectively, 49.98±10.01 and 40.42±11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values(frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00±13.32 and 41.80±15.38, 59.00±4.69 and 50.00±9.04, and 51.90±8.40 and40.09±10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow ?ow before treatment were signi?cantly decreased after treatment(P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP(all P>0.05). Conclusions: The immediate effect of STDP in treating CSF patients was apparent. This medication could signi?cantly improve coronary ?ow without affecting blood pressure or heart rate. Our ?ndings support the potential of Chinese medicine to treat ischemic chest pain.
基金Supported by the Foundation of Fujian University of Traditional Chinese Medicine(No.X2013026)the Developmental Fund of Chen Ke-ji Integrative Medicine(No.CKJ2013016)the Education Department of Fujian Province(No.JA14163)
文摘Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following Na2S2O4-induced hypoxia using Hoechst staining, annexin V/propidium iodide(PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis. Results: STP pretreatment signi?cantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by Na2S2O4 treatment(P<0.05). In addition, STP pretreatment attenuated Na2S2O4-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax,and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells(P<0.05). Conclusions: STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis.These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.
基金Supported by Zhejiang Medicine and Technology Plan(No.2018KY827)Zhejiang TCM Science and Technology Plan(No.2018ZB130)-funded Project the Study of the Protective Effects of Shexiang Tongxin dropping pill on Coronary Microcirculatory Dysfunction。
文摘OBJECTIVE:To investigate the protective effects of Shexiang Tongxin dropping pill(麝香通心滴丸,STDP)in a rat model of coronary microcirculatory dysfunction(CMD).METHODS:Sprague-Dawley rats were allocated randomly into four groups:sham,CMD model,STDP,and nicorandil.After 4 weeks of treatment,CMD was induced by injection of sodium laurate(0.2 m L,2 g/L)into the left ventricle while obstructing the ascending aorta.Rats in the sham group underwent an identical surgical procedure but were administered physiological(0.9%)saline(0.2 m L).Twenty-four hours after surgery,blood samples were collected for biochemical analyses and enzyme-linked immunosorbent assays.Heart tissues were removed for histopathology staining;apoptosis and inflammatory cytokines were examined by Western blotting.RESULTS:The STDP group had a lower level of creatine kinase-myocardial band,lactate dehydrogenase,and cardiac troponin-I than that in the CMD model group.Infiltration of inflammatory cells,myocardial ischaemia,and microthrombosis were relieved in the STDP group compared with CMD model group.Levels of endothelin-1,nuclear factor-kappa B,tumour necrosis factor-α,interleukin-6,interleukin-1β,malondialdehyde,B-cell lymphoma(Bcl)-2-associated X protein,and caspase-3 were lower,and levels of nitric oxide,Bcl-2,and superoxide dismutase were higher,in the STDP group in comparison with the CMD model group.CONCLUSION:STDP pretreatment improved the CMD induced by sodium laurate via anti-inflammatory,anti-apoptosis,and anti-oxidant mechanisms.
基金Supported by the Zhejiang Provincial Administration of Traditional Chinese Medicine(No.2018ZB082)Beijing Lisheng Cardiovascular Health Foundation of China(No.LSG1501132)Zhejiang Natural Science Foundation(No.Y15H020003)。
文摘Objective To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STDP)following sodium laurate-induced coronary microembolization(CME)in rats.Methods Forty rats were divided into 4 groups:the control(sham)group,CME group,low-dose STDP pretreatment group(20 mg·kg^(−1)·d^(−1)),and high-dose STDP pretreatment group(40 mg·kg^(−1)·d^(−1)).The rats were intragastric administrated with STDP 2 weeks before operation.Moreover,the histopathological alterations were observed using optical microscopy and transmission electron microscopy.Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay.Mitochondrial functions including the mitochondrial permeability transition pore(mPTP)mtDNA copy number were determined and proteins of AKT/GSK3βwere analyzed by Western blot.Results The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers(superoxide dismutase and catalase,P<0.01 for all).In contrast,the rats in the low-and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi(P<0.05);moreover,STDP restored the antioxidant-related protein activities and mitochondrial function,inhibited mPTP opening,decreased AKT-Ser473 phosphorylation,and increased GSK3β-Ser9 phosphorylation(P<0.05 or P<0.01).Conclusion STDP may be useful for treatment of CME,possibly via regulation of mPTP opening and AKT/GSK3βphosphorylation.
文摘目的:基于网络药理学方法探究参蛭通心胶囊核心药对人参-水蛭治疗扩张型心肌病(dilated cardiomyopathy,DCM)的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、BATMAN-TCM数据库获取人参-水蛭药对的活性成分及潜在靶点并导入UniProt数据库对所得基因进行标准化处理;运用人类基因数据库(the human gene database,GeneCards)获取DCM已知靶点;通过绘制韦恩图得到药物与疾病的交集靶点,将药物活性成分及药物-疾病共同靶点等数据导入Cytoscape 3.7.2软件,构建药物-成分-疾病-靶点网络;运用STRING数据库构建蛋白-蛋白互作网络(protein-protein interactions,PPI)并筛选出核心靶点;将核心靶基因导入基因功能注释数据库(the database for annotation visualization and integrated discovery,DAVID)平台对所得交集靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,同时利用OmicShare进行数据的可视化分析。结果:经筛选共获得人参-水蛭药对有效成分35个,药物-疾病交集靶点184个,涉及的核心靶点主要有胰岛素、白蛋白、肿瘤坏死因子、内皮一氧化氮合成酶、过氧化物酶体增殖物激活受体、白细胞介素1β等。人参-水蛭的有效成分通过对细胞膜、细胞外间隙、电压门控钙通道复合体等部位的作用、一氧化氮生物合成过程的正调控、细胞间信号传递、对凋亡过程的负调控等过程和CAMP信号通路等在内的多个信号通路协同作用治疗DCM。结论:参蛭通心胶囊的核心药对人参-水蛭可以通过参与调控多成分、多靶点、多通路治疗DCM。
基金supported by Science and Technology Commission of Shanghai Municipality(Grant No.16401972000)Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.ZY(2018-2020)-FWTX-3027)。
文摘Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is a traditional Chinese medicine to treat angina pectoris.STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice.However,whether STDP can affect platelet function remains unknown.Objective:The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention(PCI)for unstable angina.The interaction between the effects of STDP with polymorphisms of CYP2 C19 was also investigated.Design,participants and intervention:This was a single-center,randomized controlled trial in patients undergoing elective PCI for unstable angina.Eligible subjects were randomized to receive STDP(210 mg per day)plus dual antiplatelet therapy(DAPT)with clopidogrel and aspirin or DAPT alone.Main outcome measures:The primary outcome was platelet function,reflected by adenosine diphosphate(ADP)-induced platelet aggregation and platelet microparticles(PMPs).The secondary outcomes were major adverse cardiovascular events(MACEs)including recurrent ischemia or myocardial infarction,repeat PCI and cardiac death;blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme(CK-MB)and high-sensitive troponin I(hs Tn I);and biomarkers for inflammation including intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),monocyte chemoattractant protein-1(MCP-1)and galectin-3.Results:A total of 118 subjects(mean age:[66.8±8.9]years;male:59.8%)were included into analysis:58 in the control group and 60 in the STDP group.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(P>0.05)at 24 h after PCI,lower ICAM-1,VCAM-1,MCP-1 and galectin-3 at 3 months(all P<0.05)but not at 7 days after PCI(P>0.05).At 3 months,the STDP group had lower PMP number([42.9±37.3]vs.[67.8±53.1]counts/μL in the control group,P=0.05).Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers(66.0%±20.8%in STDP group vs.36.0%±28.1%in the control group,P<0.05),but not in intermediate or fast metabolizers.The rate of MACEs during the 3-month follow-up did not differ between the two groups.Conclusion:STDP produced antiplatelet,anti-inflammatory and cardioprotective effects.Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.