The Aging Process, Changes In Nitric Oxide Signaling Factors And Immunomodulatory Drugs

It is well-known that the immune function declines with aging. Previous works in our laboratory showed that the production of IL-2, IL-3, GM-CSF and NLK decreased in spleen lymphocytes from aged mice, and gene transcription of these factors was inhibited also. In this study, the signal transduction mechanisms about nitric oxide synthase(NOS) in aging were studied. The immunomodulatory effects of Achyranthes bidentata polysaccharides(ABPS) were also studied. Z-893 is a new analogue of bleomycin, which is a new antitumor antibiotic produced by Streptomyces verticillus var. pingyangensis n. var.. We also investigated the pulmonary toxicity of Z-893. In order to investigate the pathological mechanisms of pulmonary fibrosis and to evaluate the pulmonary toxicity of analogues of bleomycin, we successfully found up a pulmonary fibrosis model in mice.1. The spectrophotometry with Griess reagent was used for the determination of NO in cell suspension. A method was developed for the determination of NOS activity in biological sample by HPLC.Nitric oxide (nitrite) and nitric oxide synthase (NOS) activity were measured in cerebral cortex isolated from Wistar rats of two age groups (young: 5 months, old: 30 months). The NO content and NOS activity in old rats were shown to be significantly higher than those of young rats (P<0.01).Intrasynaptosomal calcium concentration was measured using double wavelength fluorescence spectrophotometer in cortex isolated from Wistar rats of two age groups (young: 5 moths; old: 30 months). Synaptosomes were loaded with the fluorescent dye, Fura-1/AM. Intrasnaptosomal free calcium concentration in old cortex was shown to be significantly higher than that in young cortex.Expression of bcl-2 and nNOS gene in rat brain was detected with in situ hybridization. bcl-2 mRNA expression was found is young rat hippocampus, but not in aged rat brain. nNOS expression was not found in young rat brain, but it was found in aged rat hippocampus.Expression of bcl-2 and C-myc gene in human kidney tissue was detected with RT-PCR. bcl-2 mRNA expression was found is young human kidney tissue, but not in aged human kidney tissue. RT-PCR analysis indicates that the level of C-myc mRNA is higher in aged human kidney tissue than in young human kidneytissue.