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 observe the effects of peroxisome proliferator-activated receptor (PPAR) alpha agonist Fenofibrate (FF) on energy metabolism and histology in isoproterenol (Iso) induced acute myocardial ischemic injury model.

METHODSMale Wistar rats were randomly divided into control group, Iso group (5 mg/kg, i.p.) and FF group (80 mgxkg(-1)xd(-1) per gavage for 7 days, then Iso 5 mg/kg, i.p. n = 30 each). Twenty-four hours post Iso, heart weight/body weight ratio, myocardial histopathological changes (HE staining), serum and myocardial free fatty acids (FFA) levels, the myocardial protein expression of PPARalpha (Western blot) were determined.

RESULTCompared with the control group, pathological myocardial injuries were observed under light microscope in Iso treated hearts and FF pretreatment could significantly attenuate these changes [necrotic area: 0 vs (10.00 +/- 3.00)% vs (7.36 +/- 2.60)%], the heart weight/body weight ratio, FFA in serum (501.17 +/- 43.69 vs 939.53 +/- 69.51 vs 736.53 +/- 70.30 micromol/L) and myocardium (62.01 +/- 9.19 vs 140.59 +/- 19.34 vs 116.28 +/- 14.03 micromol/L) were significantly increased while myocardial protein expressions of PPARalpha (251.57 +/- 10.95 vs 191.97 +/- 10.74 vs 215.08 +/- 9.61) was significantly downregulated in the Iso group and FF pretreatment could significantly attenuate these changes (all P < 0.05).

CONCLUSIONOur data suggested that the FFA utilization was decreased in Iso induced acute myocardial ischemic injury and FF could attenuate Iso induced myocardial damage via activating PPARalpha signaling pathway.

Animals ; Disease Models, Animal ; Energy Metabolism ; Fenofibrate ; pharmacology ; therapeutic use ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; prevention & control ; Myocardial Reperfusion Injury ; chemically induced ; metabolism ; prevention & control ; Myocardium ; metabolism ; PPAR alpha ; metabolism ; Rats ; Rats, Wistar

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

OBJECTIVETo study the molecular mechanism of effect of Sini Decoction (SND) on myocardial endothelin (MET) in myocardial ischemic rats.

METHODSSprague-Dawley rats were randomly divided into 3 groups, the normal control group, the ischemia group and the SND group. Myocardial ischemia was produced by pituitrin in the latter two groups. The content, immunohistochemical assay and gene expression of MET-1 were determined in all the three groups and compared.

RESULTSThe content of MET in the SND group was significantly lower than that in the ischemia group (P < 0.01). Immunohistochemical examination showed that MET-1 was mainly located at the cardiac muscle cells and vascular endothelial cells with the grey scale obviously lower in the ischemia group than that in the control group and the SND group (P < 0.01). While RT-PCR showed that the grey scale of PCR product band in the ischemia group was significantly higher than that in the other two groups (P < 0.01).

CONCLUSIONSND could significantly lower MET content, it may be related to the effect of SND in inhibiting MET-1 gene expression and protein synthesis.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; biosynthesis ; genetics ; Female ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; Myocardium ; metabolism ; Phytotherapy ; Pituitary Hormones, Posterior ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley

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

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 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

OBJECTIVETo study comparatively the effect of Guanxin II and its constituents, including Salvia, Red Peony root, Chuanxiong, Safflower and Dalbergia wood, in scavenging active oxygen free radical (OFR) to explore their mechanism in overcoming the experimental acute ischemic myocardial injury and protecting myocardial tissue.

METHODSThe experimental acute myocardial ischemic model was established by intraperitoneal injection of pituitrin to rats. OFR level in animal heart tissue was directly measured with low-temperature electron paramagnetic resonance (EPR) spectrometer.

RESULTSThe pathological examination of HE stained slide of myocardial tissue and electrocardiography of model animal showed that typical changes of acute myocardial ischemia occurred in myocardial tissue, EPR showed that OFR level in myocardial tissue increased abnormally. The ethanol extract of Guanxin II and its constituents could lower the increased OFR level close to normal, thus to alleviate the myocardial damage.

CONCLUSIONOverproduction of OFR could induce damage of heart tissue, its level could be measured directly using low temperature EPR. One of the molecular mechanisms of Guanxin II and its constituents in antagonizing and repairing myocardial damage is to scavenge the abnormal increased active OFR in tissue. This study has provided a basis for further studying the mechanism of Chinese composite recipes and their constituents.

Animals ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Electron Spin Resonance Spectroscopy ; Free Radical Scavengers ; pharmacology ; Free Radicals ; metabolism ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; Myocardium ; metabolism ; Pituitary Hormones, Posterior ; 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

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