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Study On The Anti-myocardial Ischemia/Reperfusion Injury Action Of Mitochondrial Protection Mechanism Of Dextran Saponin ?a

Posted on:2019-12-15Degree:MasterType:Thesis
Country:ChinaCandidate:X S LiuFull Text:PDF
GTID:2404330548453770Subject:Pharmacy
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In recent years,the incidence of ischemic cardiomyopathy continues to rise,and ischemia-reperfusion injury may occur after treatment of ischemic cardiomyopathy,which may incresed the injury of impaired myocardial and expanded the infarct size,so prevention of myocardial ischemia-reperfusion injury has also become a hot and important point in the field of cardiovascular disease in today's society.The role of mitochondria in I/R injury is getting more and more attention from the society.Mitochondria are "cell motive chambers" that play a key role in various cellular processes and are places where cells undergo energy conversion and biooxidation.More than 95%of the body's energy comes from mitochondria.Mitochondria are highly dynamic organelles and mainly include processes of mitochondrial fusion,division and autophagy.Among them,the dynamic balance between mitochondrial fusion and division is particular-ly important for the maintenance of mitochondrial function and structure.The energy supply and damaged myocardial clearance were completed with the mitochondrial fusion and split.Mitochondrial mitotic proteins are mediated by the dynamin-reLated protein 1(Drpl)and mitochondrial fission protein 1(Fisl),members of the cytosolic dynein family.Mitochondrial fusion proteins are mainly composed of the members of the membrane-anchored dynamical family Mfnl,Mfn2 and endometrial fusion Opal mediated.The dynamic balance between mitochondrial fusion and division plays a crucial role in maintaining the normal physiological activities of cardiomyocytes.Intervention with mitochondrial fusion and division may also be an important direction for the treatment of ischemic diseases.Aralia elata is a perennial deciduous tree of Wakaxia,mainly distributed in the northeastern three provinces of China.It is rich in resources and a variety of physiologically active substances,such as saponins,fats,volatile oil,can be isolated.Aralia elata saponin has anti-myocardial ischemia,anti-tumor,anti-inflammatory,cardiac and other pharmacological effects.Currently,Congmu Xinmai Tong Capsule,which is developed with the composition of Aralia total saponin for the treatment of coronary heart disease and angina,has been approved for drug clinical research(batch 2003L01111),has now completed clinical observations.Although Aralia elata total saponin has a significant protective effect on the cardiovascular system,its basic research on the cardiovascular activity of monomeric saponins is weak,seriously affecting the development and clinical application of Aralia elata.Deglucose chikusetsu saponin IVa(CE)3-0-[beta-D-pyran glucuronic acid-oleanolic acid glucoside is a monomer compound isolated from total saponins of Aralia elata.Our team has done a lot of research on the cardiovascular protective effect of CE in the early stage,and found that CE has extensive activity in the field of anti arrhythmia,cardiovascular protection and atherosclerosis in isolated rat hearts.This study will use the SD rat myocardial I/R injury model and H9C2 H/R in myocardial cell injury model to study the protective effect of CE on myocardium,and explore the protective effect of Aralia elata monomer ginsenoside CE on myocardial ischemia reperfusion injury from a new angle of mitochondrial dynamics,their signal pathway confirmed.This study demonstrated that CE preconditioning has a protective effect on H9c2 cardiomyocytes against hypoxia/reoxygenation injury and SD rat's reperfusion injury both at CEllular level and animal level,and clarified its protective mechanism.Its protective effect is related to mitochondrial energy metabolism,mitochondrial fusion and division,as well as AMPK and ERK related pathways,suggesting that maintaining mitochondrial fuction and restoring energy metabolism is a mechanism of CE against myocardial ischemia/reperfusion injury.
Keywords/Search Tags:Dextran Saponins IVa(CE), Myocardial ischemia/reperfusion(I/R), Mitochondrial fusion and division, Energy metabolism, Aralia elata
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