The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.
Animals ; Intestinal Absorption ; Intestines ; Isoproterenol ; Myocardial Ischemia/chemically induced* ; Polygonum ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo build a type 2 diabetes mellitus rat model with cardiac ischemia.

METHODSMale Wistar rats were fed high sucrose and high fat diet for four weeks and then injected with streptozoticin (STZ) (40 mg/kg .i.p.). The levels of fasting blood glucose and serum insulin were monitored every week. The body weights of rats were also measured every week. The blood levels of creatine kinase and lactate dehydrogenase (LDH) were measured following the electrocardiograph used BL-410 biological experiment system.

RESULTSThe serum insulin levels of diabetic rats were 4.05 ng/ml after four weeks high sucrose and high fat diet. The fasting blood glucose levels of diabetic rats were 17.9 mmol/L after injection. Compared with normal group, there was obvious change of S-T segment in the electrocardiograph of diabetic group at the fourteenth week. The levels of creatine kinase and lactate dehydrogenase in diabetic group significantly increased in comparison with those in normal group.

CONCLUSIONThe cardiac ischemia of diabetic rats model is suitable for investigating cardiac disease of diabetes mellitus.

Animals ; Creatine Kinase ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 2 ; chemically induced ; physiopathology ; Diet, High-Fat ; adverse effects ; Dietary Sucrose ; adverse effects ; Disease Models, Animal ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Ischemia ; physiopathology ; Rats ; Rats, Wistar ; Streptozocin

Isoproterenol (ISO)-induced myocardial ischemia animal model has been widely applied to the study of myocardial ischemia and evaluation of drug efficacy. Metabolic profiling of endogenous compounds can make a deep insight into biochemical process of the ISO-induced myocardial ischemia rats. Herein, rats were treated with ISO (2 mg x kg(-1)) for 10 days. After the model was established by measuring myocardial histopathology and plasma creatine kinase, GC/TOF-MS was used to determine endogenous metabolites in plasma and cardiac muscle of rats, and pattern recognition was used to process the data. Results showed that the plasma metabolic profiling of ISO-induced myocardial ischemia rats was significantly different from that of the control, and it had the tendency to the normal state after the discontinue of ISO injection. Besides, the cardiac muscle of rats treated with ISO for 10 days and the normal cardiac muscle could also be separated clearly. The potential biomarkers in plasma and cardiac muscle of model rats had homogeneity and their own specialty. Biochemical metabolic pathway analysis indicated that this myocardial ischemia model was involved in the alternation of energy metabolism, saccharometabolism, lipid metabolism, nucleoside metabolism and amino acid metabolism, and in relationship with oxidative stress. These findings revealed that metabonomics may be a promising tool to evaluate myocardial ischemia rat model induced by ISO and could further extend the study of pharmacodynamic action of drugs at the molecular level.
Animals ; Creatine Kinase ; blood ; Energy Metabolism ; Isoproterenol ; Lipid Metabolism ; Male ; Metabolome ; Metabolomics ; methods ; Myocardial Ischemia ; blood ; chemically induced ; metabolism ; Myocardium ; metabolism ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the therapeutic effects of Ginkgo biloba extract (EGb) in rats with acute myocardial injury induced by isoproterenol (ISO).

METHODThe rats, induced by Isoproterenol (4 mg x kg(-1) x d(-1), 10 d, sc), were divided into groups: sham, model, metoprolol (10 mg x kg(-1) x d(-1), 13 d, ig), EGb (100 mg x kg(-1) x d(-1), 13 d, ig).

RESULTThe cardiac parameters of the Model group were compromised significantly in both systolic and diastolic function. Improvement in cardiac function by EGb was significant. In model groups, plasma activities of AST, LDH, CK, HBDH, CKMB and ventricular weight index (LV and RV/BW) were elevated significantly. With the treatment with EGb and metoprolol, the enzymes and ventricular weight index were significantly ameliorated.

CONCLUSIONG. biloba extract was beneficial to cardiac performance by improving myocardium enzymes and cardiac function in isoproterenol induced myocardial injury in rats.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Hemodynamics ; drug effects ; Isoproterenol ; adverse effects ; Male ; Myocardial Ischemia ; chemically induced ; drug therapy ; enzymology ; physiopathology ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley

This study is to investigate the protective effect of urantide against myocardial ischemia injury in mice and its mechanism. The ischemic model was made by using subcutaneous injection of isoproterenol (Iso) in mice, the change of ST segment of electrocardiogram (ECG) was observed, and the activitise of lactate dehydrogenase (LDH) and nitric oxide synthetase (NOS), the contents of malonaldehyde (MDA) and nitric oxide (NO) in serum were measured. The histopathological changes of myocardium were observed by using HE staining. The anoxia/reoxygenation (A/R) model of myocardial cells on neonatal Sprague-Dawley rats was established. Methyl thiazolyl tetrazolium (MTT) assay and confocal microscopy were respectively used to measure the viability and intracellular Ca2+ concentration in myocardial cells exposed to A/R. LDH activity and cTnI content in the cell culture medium were assayed for the evaluation of myocardial cells injury. The results revealed that urantide in the range of 3 - 30 microg kg(-1) iv markedly inhibited Iso-induced raise of the ST segment of ECG; 10 and 30 microg kg(-1) significantly reduced the increases of MDA content and LDH activity in mice serum, remarkably raised the activity of NOS and the content of NO. Urantide (10 and 30 microg kg(-1)) also significantly ameliorated myocardial ischemic injury. On the A/R model of myocardial cells, urantide (1 x 10(-6) - 1 x 10(-9) mol L(-1)) could evidently inhibit the increases of cTnI content, reduce the rise of intracellular Ca2+ concentration. Urantide (1 x 10(-6) - 1 x 10(-7)) mol L(-1) increased the viability of myocardial cells injured by A/R and cut down LDH activity in the cell culture medium. Therefore urantide has significant protective effect against myocardial ischemia or A/R injury via the inhibition of Ca2+ overload and the augmentation of NO synthesis.
Animals ; Calcium ; metabolism ; Cardiotonic Agents ; pharmacology ; Cells, Cultured ; Electrocardiography ; Female ; Isoproterenol ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Mice ; Myocardial Ischemia ; blood ; chemically induced ; pathology ; Myocardium ; pathology ; Myocytes, Cardiac ; metabolism ; pathology ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Peptide Fragments ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Troponin I ; metabolism ; Urotensins ; pharmacology

Animals ; Cycadopsida ; chemistry ; Down-Regulation ; drug effects ; Female ; Flavones ; isolation & purification ; pharmacology ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; prevention & control ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the protective effect of Ophiopogonis polysaccharide (MDG-1) on isolated myocardium ischemia/reperfusion injury (IRI) and subcutaneous injection of isoprenaline induced acute myocardial ischemia.

METHODSIn ex vivo heart experiment: Langendorff guinea pigs were randomly divided into the IRI group, the fructose sodium diphosphate (FDP) group, treated with FDP 10(-6) - 10(-4) g/mL for positive control and the MDG groups treated with MDG-1 10(-6) - 10(-4) g/mL. The amplitude and frequency of cardiac contraction, coronary blood flow at different time points after ischemia reperfusion were measured. In integral animal experiments: acute myocardium ischemia model rats established by subcutaneous injection of isoprenaline were used, they were administered with MDG-1 in dosage of 10, 20 and 40 mg/kg respectively, and controlled with propranolol. Besides, a normal control group and an untreated model group for control were set up. The ST segment shift in ECG and lactate dehydrogenase (LDH) activity in serum were observed.

RESULTSEx vivo heart experiment showed that different doses of MDG-1 can increase IRI caused abnormal coronary blood flow, quickly resume the heart contraction and restrain the quickened heart rate (all P < 0.01). The integral animal experiment showed that oral administration of 40 mg/kg can reduce the increased activity of LDH in serum (P < 0.05) induced by isoprenaline, but almost had no effect on ST-segment shift in ECG.

CONCLUSIONMDG-1 can alleviate IRI isolated myocardium of guinea pigs, and oral administration of MDG-1 showed a definite protection on isoprenaline caused rats' myocardial ischemia damage.

Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electrocardiography ; Guinea Pigs ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Isoproterenol ; Male ; Myocardial Contraction ; drug effects ; Myocardial Ischemia ; chemically induced ; drug therapy ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Ophiopogon ; chemistry ; Phytotherapy ; Plant Roots ; chemistry ; Polysaccharides ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The relationship between immune vasculitis and atherosclerosis was studied. The experimental model of weanling rabbits for immune vasculitis was reproduced by intravenous injection of 10% bovine serum albumin. There were 6 groups: group A, 25 weanling rabbits with immune vasculitis subject to coronary arteriography; group B, 10 normal mature rabbits subject to coronary arteriography; group C, 10 weanling rabbits subject to coronary arteriography; group D, 8 weanling rabbits with vasculitis and cholesterol diet; group E, 8 weanling rabbits receiving single cholesterol diet; group F: 8 weanling rabbits receiving basic diet. Four weeks later, coronary arteriography was performed in groups A, B and C. The rabbits in groups D, E and F were sacrificed for the study of pathological changes in the coronary artery after 12 weeks. The results showed that the dilatation of coronary artery occurred in 6 rabbits of group A, but in groups B and C, no dilatation of coronary artery appeared. In comparison with group E, more severe atherosclerosis occurred in group D, showing the thickened plaque, fibrous sclerosis and atherosclerotic lesion. Percentage of plaques covering aortic intima, incidence of atherosclerosis of small coronary arteries and degree of stenosis of coronary arteries were significantly higher in group D than in group E (P < 0.01). No atherosclerosis changes were found in group F. It was concluded that in the acute phase, the serum immune vasculitis can induce the dilatation of coronary artery of some weanling rabbits, and aggravate the formation of atherosclerosis in rabbits fed with cholesterol diet. Immune vasculitis is a new risk factor of atherosclerosis and ischemic heart disease.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/chemically induced ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*complications ; Atherosclerosis/*etiology ; Cholesterol, Dietary/*administration & dosage ; Myocardial Ischemia/etiology ; Random Allocation ; Risk Factors ; Serum Albumin, Bovine

OBJECTIVETo explore the molecular mechanism of Wenxin Capsule (WXC, an effective Chinese composite drug) in preventing and treating myocardial ischemia of coronary heart disease.

METHODSRat model of myocardial ischemia was established by subcutaneous multi-point injecting isoproterenol. Effect of WXC on cell apoptosis was observed by transmission electron microscopy and TUNEL method, and its effect on apoptotic related gene Bcl-2 and Fas gene protein expression was observed by immunohistochemical method.

RESULTSIsoproterenol induced myocardial ischemic injury could cause evident cardial cell apoptosis, obvious enhance Fas gene protein expression and mild enhance Bcl-2 gene protein expression. WXC could significantly down-regulate Fas, up-regulate Bcl-2 gene protein expression, significantly inhibit and block the myocardial cell apoptosis.

CONCLUSIONSTo inhibit and block the event of cell apoptosis through regulating Bcl-2 and Fas gene protein expression in ischemic myocardium might be one of the mechanisms of WXT in preventing and treating myocardial ischemic injury of coronary heart disease.

Animals ; Apoptosis ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; pathology ; Myocytes, Cardiac ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; fas Receptor ; biosynthesis ; genetics

AIMTo determine the protective effect and influence on NOS expression of Montelukast sodium--a leukotriene antagonist on myocardial necrosis in rats.

METHODSMyocardial ischemia and necrosis were induced in rats by isoproterenol (2 mg.kg-1, s.c., qd for 2 d). Serum activity of LDH, CK, MDA, NO content in myocardium and scope of myocardial necrosis were measured. nNOS, iNOS and eNOS were investigated by immunohistochemical evaluation.

RESULTSDecreased serum level of LDH, CK, MDA and attenuated myocardial necrosis area were found in rats pretreated with Montelukast sodium 10 and 30 mg.kg-1. Montelukast sodium 30 mg.kg-1 also enhanced NO content in myocardium. Montelukast sodium activated the eNOS expression and reduced the iNOS expression.

CONCLUSIONMontelukast sodium is cardioprotective during myocardial injury in rats by halting the leukotrienes-induced inflammatory response and upregulating the eNOS expression as well as downregulating the iNOS expression. This may represent an approach to the treatment of myocardial ischemia with leukotriene antagonists.

Acetates ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Female ; Isoproterenol ; Leukotriene Antagonists ; pharmacology ; Male ; Myocardial Ischemia ; chemically induced ; enzymology ; pathology ; Myocardium ; metabolism ; pathology ; Necrosis ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Quinolines ; pharmacology ; Rats ; Rats, Sprague-Dawley