Study In The Relationship Between The Myocardial Aging And Glycation In The Aged Rat

Background The aging of the organisms involves the commonpathologic and physiologic processes which the elderly people are facingwith. How to defer the aging process is the hot topic in the field ofgerontology. To identify the mechanism of senility would certainly helpto prevent and treat for the old peoplperson.Objective To investigate the mechanisms of aging and senile disease, wewould demand the reliable model of aging. The natural aging model ishigher price and need long time. In the present, the artificial animalmodel of aging was developed by the international scholar. TheD-galactose aging model was established, according to the glycosylationand cross-link theory in our country. The study in the cardiovascularaging of D-gal model is seldom. Few materials showed the comparabilitybetween the D-gal and natura old animal model. In this experiment, thevariation in the cardiac structure and function was to be observed. Theultrastructure of myocardial cell, the contents of AGEs, SOD, GSH-Px,MDA and mtDNA deletion were observed. We try to approach thepathway of aging and provide the confidence of D-gal model rat. The glycosylation is higher relative with the cardiac aging, whichtriggers the oxidative stress and induces the mtDNA mutation by theAGEs formation. What would prevent and hamper the AGEs formationand improve the cardiac structure and function was the hot subject,However, the study keeps in the animal test and clinical experiment stage.The crosslink breaker,3-phenacyl-4,5-dimethylthiazolium chloride(ALT-711), improves arterial and ventricular function in older rhesusmonkeys and vascular compliance in humans. In this experiment, weobserved the changes in the cardiac structure and function and thecontents of AGEs, SOD, GSH-Px and MDA through the ALT-711administration.There were more experience to lengthen life in the traditionalmedicine. The ginkgo leaf has multiple effects and is ratified by theinternational countries. Many west countries import the ginkgo leaf andextract the oral administration or injection, then to export it. There ismuch ginkgo leaf in our country. The ginkgo leaf is extensively appliedby brain and cardiovascular patients, but seldom to be researched in themyocardial aging. In this test, we investigated the effects of ExtractGingko biloba (EGB761) to the heart aging in the rat, including naturaland D-gal aging. We observed the changes in the cardiac structure andfunction and the contents of AGEs, SOD, GSH-Px and MDA through theEGB-761 administration. Method 1. The rats were divided into young group, D-gal aging modelgroup and natural aging group, the aging model(n=10,weight200～250mg) was made by injecting D-galactose,50mg/Kg.day, and atthe same time, natural aging group group(n=10,weight 500～600mg) wasgiven the same volume NS injecting. 2. The ALT-711 administrationgroup was given ALT-711 10mg/Kg.day by intragastric administrationfor 16 weeks. 3. The EGB administration group was given EGB10mg/Kg.day by intragastric administration for 16 weeks. Themyocardial histopathological changes under electron microscope, thecontents of AGEs and oxidative mark in the cardiac tissue were measured.The mitochondrial DNA (mtDNA) deletion level in cardiac cell wasexamined using polymerase chain reaction (PCR).Results 1. D-gal and natural aging heart gained more LV weight andLA than young control group significantly (P＜0.05). The electronmicroscope showed morghology damage, including the myofilamentbreaking, dropsy mitochondria and unclear moist disc in the 2 aginggroups than the control group. The consentration of SOD and GSH-Pxwere significantly lower in the D-gal and natural aging group than that inthe control group (P＜0.05). The AGEs, MDA level in the cardiac tissuewas higher than the control group significantly (P＜0.05). The rate ofmtDNA deletion significantly increased in the 2 aging group than in thecontrol group (P＜0.05). 2. The electron microscope showed morghology improveing, including the myofilament in order, normal mitochondriaand clear moist disc in the ALT-711administration group than in theaging control group. The cardiac structure and function improved in theALT-711 administration group than in the aging control group. Theconsentration of SOD and GSH-Px were significantly higher in theALT-711 treatment group than in the aging control group (P＜0.05). TheAGEs, MDA level in the cardiac tissue was lower than in the controlgroup significantly (P＜0.05). The rate of mtDNA deletion significantlyincreased in the ALT-711 administration group than in the aging controlgroup (P＜0.05). 3. In the EGB-761 administration group, the electronmicroscope showed morghology improveing, including the myofilamentin order, normal mitochondria and clear moist disc than in the agingcontrol group. The cardiac structure and function improved in the EGBadministration group than in the aging control group. The consentrationof SOD and GSH-Px were significantly higher in the EGBadministration group than in the control group (P＜0.05) and had nodifferent with the ALT-711 group. The AGEs and MDA level in thecardiac tissue was lower than in the control aging group significantly(P＜0.05) and had no different with the ALT-711 group. The rate ofmtDNA deletion significantly decreased in the EGB administration groupthan in the control aging group (P＜0.05) and has no different with theALT-711 group. Conelusion 1. There was comparability between the D-gal and naturalaging models, which included the changes of morghology and correlatedwith nonenzymatic glycosylation and oxidative stress. The mtDNA wasinduced and results in the myocard remodel, which decrease the heartfunction.2. ALT-711 had some anti-aging effect by inhibiting NEG, reducing thefree radical and decreasing the mtDNA deletion. ALT-711 can improvethe cardiac structure and function.3, EGB had anti-aging effect by inhibiting NEG, reducing the free radicaland decreasing the mtDNA deletion.EGB can improve the cardiacstructure and function and had similar role with ALT-711.