Astragalus Polysaccharides Prevent Type 1 Diabetes Mellitus In Nonobese Diabetic Mice And Its Possible Mechanisms

Objective: Type 1 diabetes mellitus (DM) is a kind of autoimmunity disease, triggered by entironmental agents on the backround of polygenic heredity. When DM occurs, more than 90% pancreatic β cells have been destroyed, and patients have to depend on the injection of insulin all their lives, and are easy to get ketoacidosis or hypoglycemia. Its chronic complications of heart, encephalon, and kidney could also bring great pain to the patients, and even threaten their lives. Therefore, the immune intervention of type 1 diabetes mellitus with proper drugs, and the study of its possible mechanism are more significant and valuable. Type 1 DM is related with the unbalance of immunoloregulation. When the body is unable to endure the antigens of islets, both MHC-Ⅱ and its disposel antigens of β cells would activate Th1 subgroup of helper T lymphocytes (Th), and restrain Th2 subgroup, which results in the unbalance of cytokines. Then more cytotoxicity T cells (TCL), macrophages and natural killer cell (NK) are activated. And more oxygen- derived free radidicals, nitrogen monoxide (NO) and cytokines (IL-1,TNFα/β,IFN-γ)are developed. All these result in the direct toxicity on pancreatic β cells, and the occurrence of type 1 DM at last. Investigations have shown that CD4+ Th cells are the main immunal lymphocytes leading to type 1 DM. Under normal conditions, they are prosoma cells, named Thp, which only express little IL-2. When excited by specific antigens, they could be induced to Thp+ cells, which then turn into Th0 cells, prosoma cells of Th1 or Th2 cells. Th0 cells would change into Th1 subgroup when excited by INF-γ, or change into Th2 subgroup 5when excited by IL-4. Th1 subgroup mainly develops IL-1β, IL-2, IL-6,IL-12, TNF-α and INF-γ. It could conduct cellular immunity, acceleratethe maturation of Th0 cells, and depress the function of Th2 cells. Th2subgroup mainly develops IL-4, IL-5, IL-10, TGF-β. It could conducthumoral immunity, and depress the function of Th1 cells. Theequilibration of autoimmunity is maintained by these two subgroups, withtheir crossing accommodation. Th1 subgroup could accelarate the progress of type 1 DM, while Th2subgroup could provide the protection of pancreatic β cells. Theoccurrence of DM is related with the disequilibrium state of Th1/Th2subgroups and their cytokines. Nowadays, many scholars have tried toprevent the autoimmunity reaction of islets by immune interventionbefore the onset of Type 1 DM, which has become a hot spot. Commonly used agents of immune intervention on Type 1 DM couldbe devided into four groups: ① To accelerate immune reaction fromTh1-form to Th2-form, such as GAD, Hsp, FA, BCG, Vit D3, IGF-1,Anti-IL-12, etc. ② To depress the identification of T lymphocytes onantigens, such as Anti-CD3, Anti-CD4, ect. ③ To reduce the apoptosisof islets, such as nicotinamide, FasL, γ-rays, etc. ④ Genetic immunetherapy, which means to introduce the expression of immunoprotectivegenes to islets. Nowadays, more and more anti-diabetic plant componentshave been studied. Among them, polysacchrides are most important.Astragalus Polyaccharides (APS) is the uniform polysaccharide part ofAstragalus' extration, and is its main effective component. It is composedof APSⅠ,Ⅱ. APSⅠis heterosaccharide, with conformation of D-glucose,D-Galactose and L-arabinose. APSⅡis dextraven, bonded withα-(1→4)-D-glycosidic linkages. Investigations have shown that APS hasaccommodation on cellular immunity, humoral immunity, non-specificimmunity and the activity of cytokines. Our early study has shown thatAPS could decrease the blood glucose level of STZ DM mice, and give 6the protection on diabeti...