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Pine Bark Extract Proanthocyanidins Protective Effect On Cardiovascular

Posted on:2013-06-14Degree:MasterType:Thesis
Country:ChinaCandidate:J DuFull Text:PDF
GTID:2334330491963803Subject:Pharmacology
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Pine bark extract contains rich p-diphenol compound,especially procyanidins is ever found in the strongest effect of one of the free radical scavenging agents.The modern medical science has now proved that oxygen free radical and most of all human disease almost a relationship,including human mortality rates are highest disease of heart head blood-vessel.When the blood supply heart coronary artery sudden spasms,myocardial cells due to lack of oxygen and in a series of metabolic changes,myocardial cells antioxidant content decrease,into oxygen free radicals of chemical reactions due to lack of oxygen and relative speed up.In the coronary artery spasm of eliminating the moment,myocardial cells to get blood perfusion suddenly,with a large amount of oxygen into oxygen free radicals,and at the same time as the insufficient antioxidants,could not remove oxygen free radicals,the results make highly destruction oxygen free radicals seriously damaged cardiac muscle cell,a large ion by myocardial cell inside the overflow,while the latter can disrupt the control of current signal heart throb,cause ventricular fibrillation,which can cause death.Objective:Through the pine bark extract from the procyanidins,from the whole animal model and the cell level?endothelial cells?,the pine bark extract procyanidins against myocardial ischemia and pharmacological functions and mechanism,to support clinical medicine basis,for new drug development to provide pharmacodynamic basis.Methods:1.The experimental animals were divided into positive control model group,nitroglycerin group?0.083 mg/kg?,pine bark extract procyanidins low,medium and high?120.0,180.0,240.0 mg/kg?of five groups.Respectively,experiment on hypoxia tolerance in mice,against cerebral ischemia and sodium nitrite poisoning and recorded the survival time.2.Experiment on vasopressin induced myocardial ischemia:Screening of ecg normal SD rats,randomly divided into six groups,each group of eight rats.Respectively for normal control group,model control group,nitroglycerin group?0.042 mg/kg?,pine bark procyanidins low?60 mg/kg?,?90 mg/kg?,high?120 mg/kg?dose group.Among them,give the normal control group and model control group etc capacity saline.Give 1ml to fill the stomach medicine/100g,one a day,continuous 14 days.Medicine after 1 hour,the rats intraperitoneal injection?IP?respectively 10%hydration chlorine aldehyde 0.35 g/kg anesthesia.Supine fixed on the table;give the electrocardiogram machine needle electrode insert limbs subcutaneous,after the normal ? stable record united electrocardiogram,as a former value to medicine.In addition to the normal control group,the rest of the group under the tongue rats after intravenous pituitrin 0.75 U/kg,the drug has a capacity of 1.0 ml/kg and in 5 s in the injection,cause acute myocardial ischemia model,normal control group give etc capacity saline.Record 5 s,10 s,15 s,30 s,60 s,90 s,120 s ecg changes after intravenous pituitrin,simultaneous determination of serum malondialdehyde?MDA?content and lactate dehydrogenase?LDH?activity.3.Effects of pine bark extract procyanidins from on myocardial ischemia reperfusion injured rats:record ? before the league electrocardiogram,screening of ecg normal SD rats,randomly divided into six groups,each group of twenty rats.Respectively for normal control group,model control group,nitroglycerin group?0.042 mg/kg?,pine bark procyanidins low?60 mg/kg?,?90 mg/kg?,high?120 mg/kg?dose group.Among them,give the normal control group and model control group etc capacity saline.Give 1ml to fill the stomach medicine/100g,one a day,continuous 14 days.According to the literature,establish myocardial ischemia and reperfusion model and recorded the changes of ECG,determine the myocardial enzymes parameters,the scope of ischemia,pathological changes of myocardial cell apoptosis.4.At the molecular level,using human umbilical vein endothelial cells of two damage model:?Ox-LDL damage endothelial cell model;?H2O2 damage endothelial cell model.Low-density lipoproteins?LDL?are thought to become oxidized LDL?oxLDL?after undergoing oxidative modification.OxLDL exhibit a variety of biogical properties potentially involved in endothelial dysfunction,such as inducton of cell apoptosis.In vivo,we established the injury model induced by ox-LDL and medicated serum prepared by the method of serum pharmacology.Oxidative reactions induce vascular endothelial dysfunction,relating closely with the progression of atherosclerosis.In order to assess the possible supportive effect of anti-oxidation,we also studied the oxidative injury model induced by H2O2 in vitro.Results:1.Respectively,experiment on hypoxia tolerance in mice,against cerebral ischemia and sodium nitrite poisoning and recorded the survival time;effects of pine bark extract procyanidins from on myocardial ischemia reperfusion injured rats and recorded the changes of ECG in rats;experiment on acute myocardial ischemia caused by coronary artery ligation and recorded the changes of ECG,determine the myocardial enzymes parameters,the scope of ischemia,pathological changes of myocardial cell apoptosis.The results show that the pine bark extract procyanidins has the effect on hypoxia tolerance,anti-cerebral ischemia,inhibition the released of MDA and LDH,myocardial SOD activity significantly rebounded,ET-1 and IL-6 obviously decreased,have a dose dependent and statistically significant,and reduced myocardial infarct size and participation in the regulation of apoptotic proteins.2.?Procyanidins to Ox-LDL damage endothelial cell model of protection:High levels of ox-LDL have cell toxicity to HUVEC;low concentration of ox-LDL can promote cell proliferation.After Ox-LDL injured HUVEC,vigor decrease,LDH leaks out more.With contain procyanidins serum pretreatment 24h;Ox-LDL damage was reduced.Procyanidins serum containing medicine can improve cell oxidation resistance,increase the activity of SOD,reduce lipid peroxide MDA production,improve endothelial cells secrete a function,it can raise NO,PGI2 levels and reduce ET and TXA2 levels,it also can reduce the cell apoptosis.?Procyanidins endothelial cells of H2O2 damage model of protection:H2O2 can reduce the concentration dependence HUVEC proliferation activity,procyanidins serum containing medicine can increase the damage was vascular endothelial cells vigor,improve cells form,and reduce cell apoptosis,procyanidins have protection on endothelial cell,and the possible mechanism may increase the level with NO relevant.Conclusion:Pine bark extract procyanidins to myocardial ischemia have very good protection effect,it can increase SOD activity,promote endothelial cell synthesis NO,reduce lipid peroxide MDA production,restrain in ischemia ET-1 and IL-6 drops,inhibiting cell apoptosis and resist peroxidation,for the further study of the clinical trials and reference function.
Keywords/Search Tags:procyanidins, myocardial ischemia, ischemia-reperfusion, vascular endothelial cells, oxidation low density lipoprotein, H2O2
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