Research On Preventing Kidney Aging By PPAR γ Agonist

Aging of the kidney is a problem of clinical and basic interest.The glomerular filtration rate falls progressively,independent of overt pathology.Glomerular,vascular and accompanying parenchymal changes occur and other disorders associated with ageing,such as diabetes and hypertension,have a stochastic deleterious effect on both form and function.We focus our research on kidney aging to reveals the common mechanism and provide the effective measures.Present study will be based on the original research to observe the expression and the role of the PPARγduring the rat kidney aging.In the research,we attempt to document the safety and effectiveness of PPARγagonist rosiglitazone by animal experiment,and futher to explore the molecular regulation of PPARγduring the aging process.The beneficial effects of PPARγagonist antiaging can be analysized through the cellular signal transduction activities and the modulation of various redox-sensitive transcription factors.In addition,the effect of Rosiglitazone delaying kidney ageing in rat will be demonstrated by metabonomic technique and to dicover the biomarker of it.We will combine the molecular biology and metabonomics to provide a new method and pathway of preventing rat kidney aging.We made the 3month,12month and 24month natural aging rat as model which represent young,middle-aged and old group respectively.Significant expression of PPARγprotein were detected in the cell of renal tubule and collecting duct in each group by immunohistochemistry.PPARγprotein expression was observed as nuclear and cytoplasmic staining.In old age group PPARγprotein were also observed little in the mesangial cells and Bowman capsul's epithelial cell.However,hybridization in situ also verified the above result at mRNA level.Westernblot result shows that PPARγprotein decreased with age,while the activity of superoxide dismutase(SOD) and Glutathione peroxidase(GSH-PX) in rat kidney were decreased.The activity of SOD and GSH-PX were positively correlated with the expressions of PPARγ.In the second part,we designated the calorie restriction group as positive control while treated the middle-aged rat group and old rat group with RGTZ.We find the expression of PPARγprotein increased in RGTZ and CR groups in middle-aged and old rat kidney tissue compared with control group.P53 protein were no obvious different among different groups. Collecting the serum samples of each old rat group,we confirmed the chemical componds and final products of metabolism in the rat serm by HPLC/MS analysis.The results declare that the principle component score was usually distributed in several regions of the scatterplot ellipse graph,and each group has no obvious acrossing.The metabolism products are significantly different among every group.In this study,5 biomarkers were structurally proposed and all these metabolites will provide more information to study the mechanism of preventing rat kidney senescence.In addition,the lipid componds are closely connected with energy and lipid metabolism.It is conceivable that all of the differences observed here investigate that the energy and lipid metabolism in animal have changed much,and perhaps it is the potential reason to induce aging.All above were summarized as following:PPARγparticipate in the regulating of rat kidney aging.Date further revealed that PPARγagonist enhance the old animal's ability to anti-oxidative stress,reduce the expression of tumor inhibit factor P16. Preventing kidney aging of RGTZ,also provide a better understanding of the role of PPARγ,which can regulate the disorder of lipid metabolism,increase the breakdown of TG,and enhance the sensibility of insulin.