目的 探讨黄芪、山药配伍对小剂量多次链脲佐菌素( MLD-STZ)诱导糖尿病小鼠的治疗作用及相应机制.方法 以低剂量链脲佐菌素多次腹腔注射,建立糖尿病小鼠模型,将制备好模型小鼠分为山药组(1.4 g· kg-1·d-1)、黄芪组(2.8 g· kg-1·d-1)、配伍组(山药加黄芪4.2 g· kg-1·d-1)及模型组(等量蒸馏水进行灌胃),同时设立正常对照组,每周测定小鼠空腹血糖及体质量,4周后处死小鼠.形态学方法观察胰岛病理结构变化,TUNEL检测胰岛细胞凋亡,化学比色法测定血清中超氧化物歧化酶(SOD)、一氧化氮(NO)的含量；MTT测定脾细胞对刀豆蛋白A( Con A)的增殖反应,以酶联免疫吸附法(ELISA)检测脾细胞白细胞介素-4(IL-4)和γ-干扰素(IFN-γ)的分泌.结果 与模型组比较,各药物处理组对血糖的升高均有显著的抑制作用,对体质量的降低也有改善作用.胰岛病理结构显示各药物处理组均能改善胰岛病理损伤,对胰岛细胞凋亡有保护作用,其中配伍组效果明显.各药物处理组对NO均有明显的抑制作用；山药组、配伍组明显上调SOD表达；黄芪组、配伍组脾细胞对Con A的增殖能力明显减弱,同时Th1/Th2分泌因子比值下调.结论 黄芪、山药配伍能有效防治糖尿病,其机制是通过抗氧化及免疫调节共同发挥作用.%Objective To study the effects of combination therapy with Huangqi and Shanyao on MLP-STZ(multiple low dose streptozo-tocin MLD-STZ) induced diabetic mice. Methods Mouse model was established by intraperitoneal injection of multiple low dose streptozoto-cin( MLD-STZ). The diabetic mice were divided into 4 groups, and each group was intragastric administered of Shanyao( 1. 4 g ·kg-1 ·d-1) , Huangqi (2.8 g · kg -1 · d -1) , compatible Huangqi with Shanyao (4.2 g · kg -1 · d -1 ) and distilled water (4. 2 g · kg-1 · d -1 ) every day respectively. Detected glucose level and body weight every week,then the diabetic mice were killed after 4 weeks of treatment. Pancreatic histological analysis and islet cell apoptosis were measured by HE and TUNEL labeling. Activities of superoxide dismutase ( SOD) and nitric oxide( NO) in serum of the mice were detected. Proliferation ability of splenocytes to concanavalin A was tested by using MTT assay. The levels of cytokine interferon-γ( IFN-γ) and interleukin- 4( IL- 4)secreted by splenocytes were measured by enzyme linked immunosorbent assay (ELISA). Results Compared with the model group, down-regulation of glucose level and body weight occurred in all medicine treatment groups. The islet cells were protected by Huangqi and Shanyao combination treatment and the apoptosis ratio of this group were significantly decreased. All medicine treatment groups could inhibit NO production. The Shanyao group and combination group up-regulatd serum SOD significantly. The Huangqi group and combination group decreased the proliferation ability of splenocytes to concanavalin A,and down-regulated Thl/Th2 cytokine ratio. Conclusion The results showed that Huangqi and Shanyao combination could effectively prevent diabetic mouse via immunotherapeutic effects and antioxidative effect.
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