Dissertation > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)

Reperfusion cardiac effects and mechanism of total saponins of Aralia elata myocardial mitoKATP channels on rat ischemia based on

Author ChenZuoJuan
Tutor LuWeiXing
School Beijing University of Traditional Chinese Medicine
Course Traditional Chinese Medicine
Keywords aralosides ischemia reperfusion injury mito(ATP)potassium channels myocardial ischemia mitochondria replenishing qi and activating blood
CLC R541.4
Type PhD thesis
Year 2014
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Back Ground and ObjectiveCHD(coronary atherosclerotic heart disease) is one kind of common coronary disease which seriously damaged the health of humanbeings.Coronary atherosclerosis narrowed or blocked the vascular lumen, coronary athery spasmed and these functions changed, all these above caused myocardial ischemia or necrosis, then CHD happened.MI (myocardial infarction) means ischemic necrosis of myocardium. It’s arised based on coronary artery lesions, blood supply of coronary artery reduced sharply even interrupted, serious persistent ischemia leaded to revelant area myocardial infarction.MI is oen severe type of ACS (AcuteCoronarySyndrome) which had highly mortality and morbidity in China.In recent year, thrombolysis, PCI (percutaneous coronary intervention), A-CABG (Aortic-coronary artery bypass grafting) were widespread used which recanalizaed blocked coronary athery, reperfused myocardium ischemia, saved myocardial cells at the death’door, reduced infarct size, relieved myocardial remodeling, improved prognosis, savedlots of lifes who encountered acute myocardial infarction.However, sometimes reperfusion after ischemia not only coundn’t improve illness, but also exacerbated injure of functions and structures. This phenomenon named IR (ischemia reperfusion injury)based on ischemia, which showed reperfusion exacerbated unrecoverable damages of tissue.Explore mechanism of ischemia reperfusion injury, make a guarantee of recovering bloodstream of ischemic tissues as soon as possible, preventing and curing reperfusion injury is a significance task need to be solved eagerly in ischemiac disease.Aralia mandshrica is Aralia elata araliaceae plant which is rich in resources, mainly distributed the northeast of China. The rootstock, fur, lobe of aralia mandshrica were mild-natured, acrid flavor, slightly poisonous. This herb had lots of efficacies:dispelling wind and eliminating dampness, tonifying spleen for diuresis, promoting blood circulation to arrest pain, nourishing Qi and calming the nerves, securing essence and nourishing kidney.Modern research indicated, Ar (Aralsides) used as an antioxidant to cure myocardial ischemia and protect myocardium. Ar enhanced antioxidant capacity, decreased cytomembrane damage caused by free radical and lipid peroxide, enhanced activities of autioxidant enzyme, lessened production of free radical, stabilized concentration dissociate Ca in mitochondria, then protected mitochondria. Therefore, as other herbs, Ar treated ischemia reperfusion injury through multiple target points, the mechanism of action needs be more discussed. Mitochondria is important place of oxidative phosphorylation, it’s construction and function play an important role on ischemia reperfusion injury.Mitochondria ATP-sensitive potassium (mitoKATP) plaied an important role on stabilize biological membrane, maintain the function of mitochondria andmyocardial cell. Scientists found in recent years that mitoKATp is a significance target spot to cure myocardial ischemia-reperfusion injury by disparking mitoKATp.My research aimed at verifying whether Ar is the oppenerof mitoKATP and then confirming hypothesis as follow:Ar could open mitoKATp, stabilize cytomembrane of myocardial cell, regulate membrane potential of mitochondria, improve membrane permeability, reduce calcium overload, alter mitochondria ground substance content and composition (cytochrome C), promote recover respiratory function of mitochondria, reduce ATP hydrolysis, promote energy substance synthesis, protect the construction and function ofmitochondria, and then protect myocardial cell, alleviate reperfusion injury.This paper includes two portions:literature review and experimental research.literature reviewThis part inclouds evolution and use of Langendroff isolated heart retrpgrade perfusion method, angiocarpy ion channel pharmacology research about mitoKATP-Langendroff isolated heart retrpgrade perfusion method is the basis of the research, the first review summarized invention of isolated heart perfusion, principle of retrpgrade perfusion, two kinds of perfusion pattern, requirements of research, measurements of physiological parameters, misubderstandings possibly appeared, experimental designs and specialapplications. The second review embraced invention of electrophysioligy, concept of ion channels, physiological structre, characteristic, classify, mechanism of drug actions, classify of KATPp, distribution, related diseases. The third review retrospects the cognitive process of traditional Chinese Medicine to etiology and pathogenesis about CHD and myocardial ischemia-reperfusion injury, and the choice methods of different treatments based on syndrome differentiation; summarized the research progress of Chinese and Western Integrative Medicine to diagnosis and treatment about CHD and myocardial ischemia-reperfusion injury; describes the research progress of Chinese herbal compound single Chinese herb and extract monomer about their effects in myocardial ischemia-reperfusion injury, prompts that TCM has a broad application prospect on prevention and treatment of myocardial ischemia-reperfusion injury.Experimental researchObjective:(1) to explore how to protect myocardial ischemia-reperfusion injury during the acute myocardial infarction in rats;unequivocal the relationship of mitoKATP and ischemia-reperfusion injury;(2) to observe whether Ar is the opener of mitoKATP;(3) to illuminate the mechanism that how Ar cured ischemia-reperfusion injury in myocardial cell.Methods:using Langendroff isolated heart retrograde perfusion system built isolated heart retrograde perfusion models in rats, control group used K-H buffer solution constant pressure perfusion for125min; model group fabricate ischemia by ligaturing LAD30min and then K-H buffer solution reperfusion for75min; DZ(Diazoxide) group reperfued by improved K-H buffer solution contained50umol/L DZ; Ar group reperfued by improved K-H buffer solution contained5mg/L Ar;5-HD (5-hydroxydecanoate) group reperfued by improved K-H buffer solution contained100umol/L5-HD;5-HD uninted Ar group reperfued by improved K-H buffer solution contained1000umol/L5-HD for15min, and then reperfued by improved K-H buffer solution contained5mg/L Ar for60min. Evans blue, TTC dyeing to observe the proportion of myocardial infarction and ischemia, record the changes of haemodynamics, compare myocardial enzymology with each group at several moments. Cut out myocardium from apex of heart respectively sized1mm×1mm×1mm to prepara specimen for transmissionelectron microscope to observe myocardial ultrastructure and myocardial cell mitochondria ultrastruture; to extract mitochondria, R-123(Rhodamine123) dye detectmitochondrial membrane potential byflow cytometry. Results: Ar has analogous medicinal effects with DZ, which is opener of mitoKATP-They could reduce release of myocardial enzyme in the process of myocardial ischemia-reperfusion injury in rats, improve haemodynamics, protect myocardial and myocardial cell mitochondria ultrastructure and function, stabilize cytomembrane of myocardial cell during the process of ischemia-reperfusion injury. Apart of these effects could be relieved by5-HD, which works as mitoKATP paralyser always. Conclusions:Ar could protect myocardial cell during the process of ischemia-reperfusion injury through mitoKATP.

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