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1.
Article in English | WPRIM | ID: wpr-880558

ABSTRACT

OBJECTIVE@#Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD).@*METHODS@#The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.@*RESULTS@#Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications.@*CONCLUSION@#The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

2.
Article in Chinese | WPRIM | ID: wpr-905925

ABSTRACT

Objective:To investigate the effect of Shuangshen Ningxin capsules (SSNX) on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction. Method:Rats were randomly divided into a sham operation group, a model group, a nicorandil group (5 mg·kg<sup>-1</sup>), and high- (180 mg·kg<sup>-1</sup>), medium- (90 mg·kg<sup>-1</sup>), and low-dose (45 mg·kg<sup>-1</sup>) SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration, the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres (40-120 μm, about 1 000 microspheres). Twenty-four hours after modeling, left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs) left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV), cardiac output (CO), left ventricular ejection fraction (EF), and left ventricular shortening rate (FS) were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase in left ventricular pressure (LV+dp/dt<sub>max</sub>), and maximum rate of decrease in left ventricular pressure (LV-dp/dt<sub>max</sub>), and the mean arterial pressure (MAP) was calculated. Heart rate (HR) was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin T (cTnT). Western blot was used to detect the protein expression of Caspase-3, Bcl-2, and Bax, and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the area of myocardial infarction. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the myocardium. Result:As revealed by echocardiography, compared with the sham operation group, the model group showed reduced SV, CO, EF, and FS (<italic>P</italic><0.01), and increased LVIDs and LVEDV (<italic>P</italic><0.01). Compared with the model group, the SSNX groups showed increased EF (<italic>P</italic><0.05, <italic>P</italic><0.01) and FS (<italic>P</italic><0.01), and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV, and increased LVEDV, SV, and CO (<italic>P</italic><0.05, <italic>P</italic><0.01). SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, and LV-dp/dt<sub>max</sub> in the model group were lower than those in the sham operation group (<italic>P</italic><0.01), while there was no significant difference in HR. SSNX improved hemodynamics of rats, and increased SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, LV-dp/dt<sub>max</sub>, and HR as compared with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). The serum CK, LDH, CK-MB, and cTnT levels in the model group were higher than those in the sham operation group (<italic>P</italic><0.01). Compared with the model group, SSNX groups reduced serum CK, LDH, CK-MB, and cTnT (<italic>P</italic><0.05,<italic> P</italic><0.01). Compared with the sham operation group, the model group displayed increased expression of Caspase-3 protein in the myocardium (<italic>P</italic><0.01) and reduced expression of Bcl-2 protein (<italic>P</italic><0.05). The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group, and statistical difference was observed between the low-dose SSNX group and the model group (<italic>P</italic><0.05). Compared with the model group, the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium, and the statistical difference was observed in the high-dose SSNX group <italic>(P</italic><0.01). As demonstrated by the TTC staining, compared with the model group, SSNX groups showed reduced areas of myocardial infarction (<italic>P</italic><0.01). The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group. Conclusion:SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres, improve cardiac hemodynamics, reduce the area of myocardial infarction, and decrease CK, LDH, CK-MB, and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.

3.
Article in Chinese | WPRIM | ID: wpr-905068

ABSTRACT

Objective:To study the effect of Shuangshen Xionglian (SSXL) granules on vasculopathy and phosphatidylinositol 3 kinase (PI3K)/serine threonine kinase (Akt)/nitrogen oxide synthase (eNOS) signal in hyperhomocysteinemia chronic kidney disease rats. Method:Rats were randomly divided into 5 groups: sham operation group, model group, and high, medium and low-dose (8, 4, 2 g·kg-1) SSXL groups. The model of hyperhomocysteinemia chronic kidney disease in rats was established with high methionine feed combined with 5/6 nephrectomy. After 5/6 nephrectomy, continuous intragastric administration lasted for four weeks. Arterial blood pressure was measured at the 4th and 8th weeks after operation. At the end of the 8th week after the operation, blood was collected to determine serum creatinine, urea nitrogen, homocysteine (Hcy), methionine and blood lipid. Western blot was used to detect the expressions of PI3K/Akt/eNOS pathway-related proteins, such as p-p85, p-Akt and p-Ser177 in thoracic aorta, and serum NO and eNOS were measured. The changes of endothelium-dependent relaxation and non-endothelium-dependent relaxation were measured by the method of isolated thoracic aorta ring. Pathological htoxylin eosin (HE) staining was used to observe the changes of renal tissue and thoracic aorta. Result:At the 8th week of the experiment, compared with the sham operation group, arterial systolic blood pressure, serum urea nitrogen, creatinine, Hcy, methionine, total cholesterol and low-density lipoprotein of the model group were significantly increased. Four weeks later after administration, arterial systolic blood pressure, serum urea nitrogen, Hcy, methionine, serum total cholesterol and serum low-density lipoprotein were significantly reduced in each dose group (P<0.05, P<0.01). The creatinine in the SSXL 8, 4 g·kg-1 group was significantly reduced (P<0.05). The nitric oxide content of SSXL in each dose groups were increased compared with that in the model group (P<0.05, P<0.01), and the serum eNOS activity of the SSXL in the SSXL 8 g·kg-1 group was significantly increased compared with that in the model group (P<0.05). The endothelium dependent and non-endothelium dependent vasodilation of thoracic aortic rings in the model group were significantly damaged. The cumulative concentration of acetylcholine (1×10-5.5~1×10-4 mmo1·L-1) in the SSXL 8 g·kg-1 group was significantly improved (P<0.05, P<0.01). The diastolic degree of the vascular ring in the SSXL 8 g·kg-1 group was significantly higher than that in the model group (P<0.05). Western blot results showed that the expressions of p-85, p-Akt and p-Ser177 in blood vessels increased in the sham group compared with those in the model group (P<0.01). Compared with the model group, the phosphorylation level of this pathway was increased in the SSXL groups, and the expressions of p-Akt and p-Ser177 in the SSXL 8 g·kg-1 group were significantly increased (P<0.05). The pathological results showed that the pathological changes of thoracic aorta and renal tissue in the dosages of SSXL were significantly reduced compared with those in the model group. Conclusion:SSXL granules can improve hyperhomocysteine and dyslipidemia in rats of chronic kidney disease with hyperhomocysteine, reduce serum creatinine, urea nitrogen levels and arterial systolic blood pressure, and improve vascular morphology and diastolic function, which may be related to the regulation of the PI3K/Akt/eNOS signaling pathway.

4.
Article in Chinese | WPRIM | ID: wpr-887994

ABSTRACT

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.


Subject(s)
Angina Pectoris , Angina, Unstable/drug therapy , China , Drugs, Chinese Herbal , Humans , Network Meta-Analysis , Treatment Outcome
5.
Article in Chinese | WPRIM | ID: wpr-921663

ABSTRACT

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.


Subject(s)
Blood Platelets , Coronary Disease , Humans , Medicine, Chinese Traditional , Platelet Activation , Syndrome
6.
Article in Chinese | WPRIM | ID: wpr-828385

ABSTRACT

Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.


Subject(s)
Autophagy , Humans , Medicine, Chinese Traditional , Myocardial Ischemia , Myocardium , Myocytes, Cardiac
7.
Article in Chinese | WPRIM | ID: wpr-828061

ABSTRACT

The aim of this paper was to investigate whether the mechanism of salvianolic acid B in protecting H9 c2 cardiomyocytes from hypoxia/reoxygenation injury is related to the regulation of mitochondrial autophagy mediated by NIX. H9 c2 cardiomyocytes were cultured in vitro and divided into normal group, model group and salvianolic acid B group(50 μmol·L~(-1)). Hypoxia/reoxygenation injury model was established by hypoxia for 4 h and reoxygenation for 2 h. In normal group, high glucose DMEM medium was used for culture. Those in model group were cultured with DMEM medium without glucose and oxygen, and no drugs for hypoxia and reoxyge-nation. In salvianolic acid B group, salvianolic acid B prepared by glucose-free DMEM medium was added during hypoxia, and the other process was as same as the model group. The cell viability was evaluated by CCK-8 assay. The leakage of lactate dehydrogenase(LDH) was detected by microplate method. The levels of intracellular reactive oxygen species(ROS) and mitochondrial membrane potential(ΔΨm) were measured by chemical fluorescence method. The level of intracellular adenosine triphosphate(ATP) was mea-sured by fluorescein enzyme method. The autophagy related proteins LC3-Ⅰ, LC3-Ⅱ, apoptosis related protein cleaved caspase-3 and mitochondrial autophagy receptor protein NIX were detected by Western blot. As compared with the normal group, the activity of H9 c2 cardiomyocytes and ATP level were decreased(P<0.05); LDH leakage and ROS production were increased(P<0.01); ΔΨm was decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio, cleaved caspase-3 and NIX protein expression levels were increased(all P<0.05) in the model group. As compared with the model group, the activity of cells and ΔΨm were significantly increased(P<0.01); ATP level was increased(P<0.05); LDH leakage and ROS generation were decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio was decreased(P<0.01); cleaved caspase-3 and NIX expression levels were decreased(P<0.05) in the salvianolic acid B group. The protective effect of salvianolic acid B on hypoxia/reoxygenation injury of H9 c2 cardiomyocytes may be associated with inhibiting mitochondrial auto-phagy. The specific mechanism may be related to inhibiting the activation of mitochondrial autophagy mediated by NIX, increasing ΔΨm, reducing ROS production, reducing the expression of cleaved caspase-3, LC3-Ⅱ, and increasing cell viability.


Subject(s)
Apoptosis , Autophagy , Benzofurans , Cell Hypoxia , Cell Survival , Humans , Hypoxia , Myocytes, Cardiac
8.
Article in Chinese | WPRIM | ID: wpr-873191

ABSTRACT

Objective:To observe the effect of Shuangshen Ningxin capsule in alleviating myocardial ischemia/reperfusion injury in rats by regulating mitochondrial adenosine triphosphate(ATP)-sensitive potassium channels.Method:A total of 56 adult male Sprague-Dawley rats were randomly divided into sham-operated control group (sham), model group (model), Shuangshen Ningxin group (SSNX, 90 mg·kg-1).Shuangshen Ningxin and mitochondrial ATP-sensitive potassium channel (MitoKATP) channel inhibitor group 5-hydroxyl-acid group (SSNX+5-HD, 5 mg·kg-1), with 14 rats in each group. Except the sham operation group, the other three groups received occlusion of left anterior descending coronary artery (LAD) for 45 min, and were sacrificed 3 h after reperfusion. Myocardial ischemia and infarct size were observed by TSC Evans blue staining, and myocardial tissue damage degree was observed by hematoxylin-eosin(HE) staining. The kit was used to measure serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The ultrastructural changes of mitochondria and mitochondrial autophagy were observed under transmission electron microscope. The changes of mitochondrial membrane potential in cardiomyocytes were detected by fluorescent probe.Result:Compared with the sham group, myocardial infarct size and myocardial ischemic area percentage in the model group were significantly increased, myocardial tissue arrangement was disordered and loose, individual myocardial fibers were broken, cardiomyocytes were necrotic, and serum CK, CK-MB, LDH activities were significantly increased (P<0.01). Mitochondrial membrane potential was significantly decreased (P<0.01), and mitochondrial structure was destroyed by transmission electron microscopy. Compared with the model group, the myocardial tissue of the SSNX group was arranged orderly, and a small amount of cell edema was mildly degenerated. The percentage of myocardial infarct size and myocardial ischemic area was significantly decreased, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), while mitochondrial membrane potential increased (P<0.01). Compared with the model group, the SSNX+5-HD group had mild myocardial tissue disorder and mild degeneration of cell edema in some areas, the percentage of myocardial infarct size and myocardial ischemic area was significantly reduced, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), and mitochondrial membrane potential increased (P<0.01). Compared with SSNX group, SSNX+5-HD group had significant increase in serum CK, CK-MB and LDH activities (P<0.01), significant increase in the percentage of myocardial infarct size and myocardial ischemic area, and mitochondrial membrane potential Reduced (P<0.05).Conclusion:SSNX protects rat myocardial ischemia-reperfusion injury by opening mitochondrial ATP-sensitive potassium channel.

9.
Article in English | WPRIM | ID: wpr-328509

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of salvianolic acid A (SAA) on L-type calcium current (I-CaL) in isolated ventricular myocytes of Sprague-Dawley rats.</p><p><b>METHODS</b>SAA powder was dissolved in normal Tyrode's solution to reach the concentrations of 1, 10, 100, and 1000 μmol/L. The traditional whole-cell patch-clamp recording technique was employed to evaluate the effects of SAA on I-CaL in single ventricular myocytes which were prepared by Langendorff perfusion apparatus from Sprague-Dawley rats.</p><p><b>RESULTS</b>SAA (1, 10, 100, and 1000 μmol/L) inhibited I-CaL peak value by 16.23%±1.3% (n=6, P<0.05), 22.9%±3.6% (n=6, P<0.05), 53.4%±3.0% (n=8, P<0.01), and 62.26%±2.9% (n=6, P<0.01), respectively. SAA reversibly inhibited I-CaL in a dose-dependent manner and with a half-blocking concentration (IC(50)) of 38.3 μmol/L. SAA at 100 μmol/L elevated the I-V curve obviously, and shifted the half-active voltage (V(0.5)) from (-15.78±0.86) mV to (-11.24 ±0.77) mV (n=6, P<0.05) and the slope (K) from 5.33±0.74 to 4.35±0.74 (n=6, P>0.05). However, it did not alter the shapes of I-V curve, steady-state inactivation curve, or recovery from inactivation curve.</p><p><b>CONCLUSIONS</b>SAA inhibited I-CaL in a dose-dependent manner. It shifted the steady-state activation curve to a more positive voltage, which indicated that the drug affected the activated state of calcium channels, and suggested that the Ca(2+) antagonistic effect of SAA be beneficial in the treatment of myocardial ischemia reperfusion injury.</p>


Subject(s)
Animals , Caffeic Acids , Chemistry , Pharmacology , Calcium Channel Blockers , Chemistry , Pharmacology , Calcium Channels, L-Type , Physiology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Chemistry , Pharmacology , Lactates , Chemistry , Pharmacology , Myocardial Ischemia , Drug Therapy , Myocytes, Cardiac , Physiology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Drug Therapy
10.
Article in Chinese | WPRIM | ID: wpr-326664

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of the separate and joint use of salvianolic acid B (SalB) and tetrahydropalmatine (THP) on the L-type calcium channel of rat ventricular myocytes.</p><p><b>METHODS</b>Single isolated ventricular myocytes of rats were obtained using acute enzymolysis separation. The current of the L-type calcium channel was recorded using whole-cell patch clamp technique. Changes of the current peak value of the calcium channel (the vertical distance between the peak value point after activation of the calcium electric current and the electric current track after complete inactivation) were observed before and after medication.</p><p><b>RESULTS</b>The inhibition rate of using SalB (at the dose of 1, 10, and 100 micromol/L) alone on the current peak value of the calcium channel was respectively (25.3 +/- 16.4)% (n=4), (44.6 +/- 24.0)% (n=6), and (86.0 +/- 20.4)% (n =4). That of using THP (at the dose of 10, 30, and 100 micromol/L) alone on the current peak value of the calcium channel was respectively (22.2 +/- 6.4)% (n=5), (27.4 +/- 1.6)% (n= 3), and (51.0 +/- 23.0)% (n=9). The inhibition potency of joint use of SalB (1 micromol/L) and THP (10 micromol/L) on the current peak value of the calcium channel was stronger than using SalB (1 micromol/L) alone or THP (10 micromol/L) alone, showing statistical difference ( P< 0.05). Atropine hydrochloric acid (14 mmol/L) could reverse the inhibition of THP on the L-type calcium channel, while strengthening the inhibition of SalB.</p><p><b>CONCLUSIONS</b>Both SalB and THP showed inhibition on the L-type calcium channel of rat ventricular myocytes. They could generate synergistic effects. Besides, their action mechanisms for regulating the L-type calcium channel were different.</p>


Subject(s)
Animals , Benzofurans , Pharmacology , Berberine Alkaloids , Pharmacology , Calcium Channels, L-Type , Metabolism , Heart Ventricles , Cell Biology , Male , Myocytes, Cardiac , Metabolism , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley
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