ABSTRACT
OBJECTIVE: To study the immunomodulatory effects of Astragalus polysaccharide (APS) in type 1 diabetic mice. METHODS: A mouse model of type 1 diabetes mellitus was established by intraperitoneal injection of multiple low dose streptozotocin (MLD-STZ). The diabetic mice were intraperitoneally administered 100, 200, 400 mg/kg APS or 1 ml normal saline (NS) every day respectively, then the diabetic mice were sacrificed after 15 or 30 days of treatment. The effect of APS on insulitis was determined via pancreatic histological analysis. Serum insulin autoantibody (IAA) levels were measured by radio-immunoassay (RIA). Proliferation ability of splenocytes to concanavalin A was tested by using [(3)H] thymidine incorporation assay. The levels of cytokine interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) secreted by splenocytes were determined by enzyme linked immunosorbent assay (ELISA) method, and the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in spleens was characterized using Western-blot analysis. RESULTS: Attenuated insulitis, down-regulation of the serum IAA levels and Th1/Th2 cytokine ratio, decrease of the proliferation ability of splenocytes to concanavalin A, and up-regulation of the PPARgamma levels in spleens showed a significant time- and dose-dependent response to APS treatment as compared with the NS-treated group. CONCLUSION: APS possesses immunotherapeutic effects on mice with type 1 diabetes mellitus through improving the cell- and humoral-mediated immunity.
ABSTRACT
The animal experiment studies have demonstrated that hyperthermia is a strong teratogen to many kinds of animal with high incidence of neural tube defects(NTD).Epidermiological investigation showed that hyperthermia was closely related to the acencephaly and excenphaly in human being,but little was known about the distinct mechanism of NTD induced by hyperthermia.In order to study the developmental mechanism of NTD induced by hyperthermia,we observed the effects of hyperthermia on the neuroepithelial cells in primary culture.The neural tubes of the hamster embryos on 10 d after fertilization were obtained.the neuroepithelia were dissociated and then seeded at the density of 1×106 cells per well.The cells were divided into experimental and control groups randomly.The experimental groups were exposed to 42 C for 20 min,whereas groups exposed to 37 Cserved as control.After treatment of hyperthermia,the cells were incubated continuously at 37 C in a 95%air/5%CO2 humidified incubator,the culture was terminated after different intervals.Phase-contrast microscopy.scanning electron microscopy.transmission electron microscopy,MTT assay,agarose gel electrophoresis analysis,TUNEL detection,immunocytochemistryand image analysis were made.The results of the experimental groups indicated that the floating cells and apoptotic cells increased in number,the neurites of the cells were shortened even disappeared,the survival cells decreased in number,the ultrastructure of the cells demonstrated distinct abnormal changes,the function of mitochondria was impaired,the expressions of both bcl-2 and bax were abnormal.The above results suggest that hyperthermia may induce apoptosis of neuroepithelial cells,duringwhich bcl-2 and bax genes may play important regulatory roles.