Study On The Injury Of Liver MtDNA Of Mice Induced By D-galactose

The "Aging" is a natural law, which can not be resisted. Delaying aging or prolonging life is a dream of human all the time. For the past few years, population-aging problems are becoming more and more serious in our nation. To prevent and treat diseases related to aging it has been widely attented. The research of aging is becoming more and more important. With wide attention, the theoretics hypothesis on aging emergence was brought forward in academic fileds. Different aspects researches generate different theories of aging. Each theory has its reasons and evidences. The history of aging researching tells us, it's very hard to sum up all aspects. Different theories have relations with each other. In the research of the aging, it's a tough problem to build an animal model. The aging animal model is very essential in the study of the mechanism of aging and the searching of the anti-aging medicine. More and more researchers notice that the subacute aging model can be induced by the high dose D-galactose injection. Many kinds of the aging appearances, even the special appearances can be observed in the aging model mice induced by D-galactose injection. The study of the aging model is not very complete and the mechanism is not very clear. Now, the "mitochondrial- FR-mtDNA" theory is gradually accepted by more and more researchers. So, it has veryimportant value to eshtablish an aging animal model induced by high dose D-galactose injection identified by investigating the relationship of the common deletion of the mtDNA, and the activities of the anti-oxidases and respiratory enzymes. The results can be well referenced in the research of aging associated diseases, such us tumor, angiocardiopathy, diabetes, AZ, cataract and so on.In this study, subacute aging animal model was established by D-galactose (0.1mg/g. bw) hypodermic injection into scruff, once a day for 45 days. The reliability of the animal model is ascertained by measuring the aging associated criterions, especially, special aging criterions. Aging inducing damage effect of D-galactose is investigated through the research. The results showed that the positive blue granules appeared in cells by SA-β-Gal staining were found in the aging mice model's hepatic cells of lobule circumambience and endothelial cells of brain membrane. The 3866bp common deletion in the liver mtDNA had been observed in aging mice model. MDA, an important oxidative criterion, increase significantly in the model group. The mitochondrial's respiration functions were improved. The activities of the NADP oxidase (NADHOX) and the sucinic acid oxidase (SUCOX) are increased, compared with those of control group.The results also showed that there was deletion damages of the mtDNA happened in the model animal mitochondrial. The damages associate with the oxidative stress generated by the FR damage. The oxidative stress damages in the mitochondrial resulted in the increase of the respiratory function compensated.FR is active molecule and can induce the mitochondrial DNA damages, which is important one of the mechanism in the aging animal model. The research has elementary proved ths supposing in molecule level. The compensated increasing of the respiratory enzymes is the main feature of this kind of damage. It shows the slow-moving processof aging. The increasing of the respiratory enzymes reflects some feed back mechanisms that increase the functions of the remaining mitochondrial compensated. The result is to improve the function of OXPHOS. Single mitochondria can produce more ATPs to suffice the energy requirements of the cells. At the same time, the decreasing of oxygen's utilization rate (oxygen uptake) causes the production of ROS and the damages of mtDNA. Thus, the productions of ROS have a vicious cycle with the oxidative damages of mtDNA. Aging is a result of accumulating of oxidative damages.Vitamin C (Vc) is a sort of water-soluble antioxidant. It's the main antioxidation is in the extra-cellular fluid. It plays a very important role in antioxidation and anti-aging. High dose Vc is applied in this study to investigate the aging mechanism in the model induction. The result showed that Vc improved the life quality of the aging model mice. Compared with the control group, Vc protected-group mice had a better life condition and a lower oxidative damages level. Their anti-oxidases were not induced; their mitochondrial respiration functions were in good state: the activities of the NADHOX and SUCOX were increased significantly. But the criterions of aging which reflect the biology age, such as the common deletion of the mtDNA, the SA-β-Gal staining, were not be improved.The research inspects versatility changes of the aging induced by the oxidative damage factors in two aspects, and investigates the relationship between the common deletion of the mtDNA, and the activities of the anti-oxidases and respiratory enzymes. The studing result explains the meaning of the" Aging-mitochondrial doctrine" in the aging animal model. It provides references for further research in aging. CONCLUSION: 1. The eshtablishment of the subacute aging mice model is...