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Lymphocytes Gene Expression Profiles Reveal The Molecular Mechanisms Underlying Remodeling Effects Of Epimedium Flavonoids On Immune Homeostasis In Aged Rats

Posted on:2004-01-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ChenFull Text:PDF
GTID:1104360122955181Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Background and Objectives:The classical view of "immunosenescence" has envisaged a generalized, inexorable, age-related, unidirectional decline in immune system. And immunosenecence closely linked to increased risks of infection and higher incidence of malignancies and autoimmune disorders. Immunosenescence increases the morbidity and mortality of such kind of diseases as well. At the same time, immunosenescence is one of the most important parameters when it is referred to lifespan prognosis. The imbalance of immunological homeostasis accompanies immunosenescence. During immunosenescence, the number and function and the proliferative capability of immune cells decrease accordingly. The successful remodeling of immune system during aging will reduce the morbidity and mortality of related highly risky diseases and improve the life quality of old subjects and extend the life expectancy of the elderly. Apoptosis is of particular interest in aging, as it is thought to play an important role in various age-related degenerative diseases. There are many evidences suggest that excessive apoptosis and increased susceptibility to apoptotic stimuli play so important roles in unbalanced immune homeostasis accompanying immunosenescence. Apoptosis could be one reason for the decrease of the total number of lymphocytes and the decrease of the immune response with aging related to cancer, infections, and autoimmune disorders.The development of molecular biology reveals that apoptosis is controlled by networks of apoptosis-related genes and signal transduction pathways. And there existimportant and strong interplay and crosstalk between these regulatory mechanisms. So the knowledge of apoptosis and its underlying mechanisms not only help make clear of the etiology and pathology of a given disease, but also they can benefit the endeavor of looking for possible modulating means targeting apoptosis and its related mechanisms.Although we have learned something about immunosenescence and apoptosis as well as the possible underlying mechanisms with respect to them, we still lack the efficient ways to solve those problems surrounding immunosenescence such as the unbalanced relationship between apoptosis and proliferation. And this offers a good chance for us to probe the possible effects of natural products that have been studied and proved to be effective clinically in China for thousands of years. So we tried to analyze the spontaneous apoptosis in aged control rats, young control rats as well as a group of aged rats treated with Epimedium Flavonoids, an extract from Epimedium that has been proved to be effective on improving vigor and elongating lifespan in Traditional Chinese Medicine. We also further our study by screening the constitutive expression of genes that may display disregulated expression during aging in all these groups. As for the former experiment, we applied Flowcytometry combined with FITC conjugated Annexin V-PI double stain to measure the apoptosis percentage. And as for the latter, we applied gene chip from Affymetrix to array the gene expression profile and compare the differentially expression genes between old contral and young control as well as old control and Epimedium Flavonoids treated rats. The main purpose of our study is to elucidate the gene expression background of lymphocyte in aged rats and in the mean time, to try to find the possible target genes that Epimedium Flavonoids may touch. So in the end, we hope that our study may offer helpful hints for revelation of action mechanisms of Epimedium Flavonoids underlying the immune homeostasis during aging.Methods and Results:1,We measured the apoptosis percentage of lymphocytes from aged control rats, young control rats as well as Epimedium Flavonoids treated rats using Flowcytometry combined with FITC conjugated Annexin V-PI double stain. The quantitative results told us that the apoptosis percentage of lymphocytes from old control rats was significantly higher than those from young control rats and the p value is lower tha...
Keywords/Search Tags:Immunosenescence, Lymphocyte, Apoptosis, Gene Expression Profile, Epimedium Flavonoids
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