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Protective Effects Of Panax Notoginsenoside Rb1 And Rg1 Preconditioning On Angiotensin Ⅱ Induced Hypertrophied Neonatal Rat Myocytes Against Hypoxia-reoxygenation Injury And Effect Of Panax Notoginsenoside Rg1 On Thans

Posted on:2004-05-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:X W ZhangFull Text:PDF
GTID:1104360092495550Subject:Cardiovascular pharmacology
Abstract/Summary:PDF Full Text Request
Adaptive response (AR) is a kind of mechanism which are generally favior of the healthy body, which include many aspecets such as cardiovascular system diseases, ratio therapy in tumors,etc. Ischemic preconditioning(IPC) and Pharmacological preconditioning are currently the most effective adaptive response which being a powerful experimental strategy known for protecting myocardial ischemia.This paper was divided two parts, as follwos: 1. Cardioprotective effects of Panax notoginsenoside Rbi and Rgi onangiotensin II -induced hypertrophy of neonatal rat myocytesagainst hypoxia-reoxygenation injury.Myocardial ischemia is a common disease harmful for cardiovascular system, in which the major anatomical response of the heart is myocyte hypertrophy. Left ventricular hypertrophy (LVH) is a common consequence of hypertension, clinical and experimental evidencesuggested that Left ventricular hypertrophy(LVH) was considered to be an independent risk factor of developing ischemic heart disease, myocardial infarction, heart failure, arrhythmias and sudden cardiac death. Hypoxia/reoxygenation (H/R) plays an important role in myocardium ischemia and reperfusion injury, and hypertrophied myocardium is more susceptible to injury from ischemia than normal myocardium, therefore the study of protective effective on hypertrophied myocardium in ischemic and reperfusion injury has important clinical significance,Panax notoginsenoside Rbi and Rgi have the same chemical structures with ginsenoside Rbi and Rgi which are the main active principles of traditional Chinese medicine Panax notoginsen. Pharmacological study hasuggested that ginsenosides Rbi and Rgi hasve extensive effect of regulation and adjustment to organism including enhance the anti-stress ability of organism, strengthen the anoxia endurance, improve blood perfusion of myocardia and prevent ischemia injury against brain and cardiac ischemia. Pharmacological preconditioning are currently the most powerful experimental strategy known for protecting myocardial ischemia, which can be triggered through a number of endogenous mediators such as adenosine, nitroglycerin, endogenous nitric oxide (NO), monophosphoryl lipid A, angiotensin-converting enzyme inhibitors.As the hypoxia/ reoxygenation (H/R) injury in cultured cardiomycytesis similar to the ischemic and reperfusion (I/R) injury in animals experiment, this study investigate whether the H/R injury in hypertrophied myocardium could be protected after pretreatment with Rb1 and Rg1.Hypertrophied cardiomyocytes were induced in cultured neonatal Wistar rats by coincubated with Ang II 0.1 (o,mol/L for Id. The H/R model was established after treatment with Rb1 and Rg1 for 48h. Under confocal microscopy, the cell surface area of cardiomyocytes was measured, and total protein content in myocytes in medium were measured by biochemical methods The results showed that pretreatment with Rb] and Rg1 (0.01-10umol/L) respectively markedly reduced the cell surface area in concentration-dependent manner,with maximal effect of 41.56 % and 47.92 % (P<0.01), respectively. The total protein content was lowered by 44.28 % and 46.08 % (P<0.01), respectively. This result indicated that pretreatment of Rb| and Rgi could protect Ang II-induced myocardial hypertrophy against H/R injury in a concentration dependent manner.Lactate dehydrogenase (LDH) is located mainly in the cytoplasm and its leakage to extracellular space indicates cell death, the activities of LDH in medium were measured, the results showed that LDH activity was reduced by Rb1 and Rg1 (0.01-10 umol/L) with maximal effect of 53.06 % and 57.14 % (P<0.01), respectively; In the present study , Rg,and Rb|. could decrease LDH leakage by H/R , which was in favor of reducing cardiomyocyte hypertrophy.Several studies have shown that preventing apoptosis was one of the mechanisms in preconditioning against H/R injury. In the present study, the apoptotic rate was assayed by flow cytometry with PI staining method. Rbi and Rgi significantly reduc...
Keywords/Search Tags:hypoxia-reoxygenation
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