The immunotherapeutic effects of Astragalus polysaccharide in type 1 diabetic mice

被引:55
作者
Li, Ru-Jiang
Qiu, Shu-Dong [1 ]
Chen, Hong-Xia
Tian, Hong
Wang, Hai-Xu
机构
[1] Xi An Jiao Tong Univ, Sch Med, Minist Educ, Dept Histol & Embryol,Key Lab Environm & Genes Re, Xian 710061, Peoples R China
[2] Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China
关键词
Astragalus polysaccharide; type 1 diabetes mdlitus; Th1; Th2; PPAR gamma;
D O I
10.1248/bpb.30.470
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study investigated whether Astragalus polysaccharide (APS) possessed immunotherapeutic effects on type 1 diabetes mellitus. Diabetic mice induced by multiple low dose streptozotocin (MLD-STZ) were administered either APS (100, 200, 400 mg/kg body weight) or saline intraperitoneally daily, and sacrificed after 15 or 30 d of treatment. Meanwhile normal mice not treated with STZ nor with APS were offered into non-diabetic group. Blood glucose and serum insulin levels were measured, histologic and morphometric analyses of the pancreas were performed to determine the effect of APS on pancreatic islets. Further investigations on immune changes in spleens were tested by ELISA, semi-quantitative RT-PCR and Western blot. Downregulated blood glucose level, upregulated serum insulin concentration, increased beta cell mass, decreased apoptotic beta cell percentage, downregulation of Th1/Th2 cytokine ratio and upregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) gene expression in spleens were significantly time- and dose-dependent on APS treatment, when compared to saline controls. These results show that APS seems to be helpful to attenuate insulitis and preserve beta cells from apoptosis, but it can't entirely rescue type 1 diabetes mellitus. APS ameliorates both the clinical and histological parameters of the MLD-STZ induced diabetic mice in a long-lasting fashion, most likely through immunoregulatory actions on Th1/Th2 cytokine ratio, strongly associated with PPAR gamma gene expression in spleens.
引用
收藏
页码:470 / 476
页数:7
相关论文
共 36 条
[1]   Pathophysiology of immune-mediated (type 1) diabetes mellitus - Potential for immunotherapy [J].
Abel, M ;
Krokowski, M .
BIODRUGS, 2001, 15 (05) :291-301
[2]  
Bedir E, 2000, BIOL PHARM BULL, V23, P834, DOI 10.1248/bpb.23.834
[3]   Peroxisome proliferator-activated receptor-γ-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis [J].
Bright, JJ ;
Natarajan, C ;
Muthian, G ;
Barak, Y ;
Evans, RM .
JOURNAL OF IMMUNOLOGY, 2003, 171 (11) :5743-5750
[4]  
Cameron MJ, 1997, J IMMUNOL, V159, P4686
[5]  
CHEN W, 2001, J FUDAN U, V28, P57
[6]  
Chen Wei, 2004, Fudan Xuebao (Yixuekexueban), V31, P607
[7]   Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats [J].
Cui, R ;
He, JC ;
Wang, BE ;
Zhang, FK ;
Chen, GY ;
Tin, SS ;
Shen, H .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2003, 51 (01) :75-80
[8]   Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors [J].
Cunard, R ;
Ricote, M ;
DiCampli, D ;
Archer, DC ;
Kahn, DA ;
Glass, CK ;
Kelly, CJ .
JOURNAL OF IMMUNOLOGY, 2002, 168 (06) :2795-2802
[9]   TH1-TH2:: a Procrustean paradigm [J].
Gor, DO ;
Rose, NR ;
Greenspan, NS .
NATURE IMMUNOLOGY, 2003, 4 (06) :503-505
[10]  
Gosset P, 2001, EUR J IMMUNOL, V31, P2857, DOI 10.1002/1521-4141(2001010)31:10<2857::AID-IMMU2857>3.0.CO