穿心莲内酯衍生物对2型糖尿病大鼠的降糖作用及机制研究  

Hypoglycemic effect of andrographolide derivatives for type 2 diabetic rats

作　　者：李珍珠[1] 燕军[2] 张高小[1] 张在军[1] 于沛[1] 徐立朋[1] 

机构地区：[1]暨南大学药学院新药研究所,广州510632 [2]胜利油田孤岛医院药剂科,山东东营257231

出　　处：《中南药学》2014年第1期10-13,共4页Central South Pharmacy

基　　金：国家自然科学基金-广东省联合基金(No.U1032007);国家自然科学基金资助项目(No.81001683);高等学校博士学科点专项科研基金资助课题(No.20104401120003);教育部留学回国人员基金(No.23610008);广东省企业科技特派员工作站建设项目(No.2011B090600033);暨南大学科研培育与创新基金(No.21611433)

摘　　要：目的探讨穿心莲内酯衍生物AL-1和NDS对2型糖尿病大鼠的降血糖作用及机制。方法雄性SD大鼠给予高脂饲料喂养,给予链脲佐菌素(STZ,ip,35 mg·kg-1)诱导2型糖尿病大鼠模型,给药1周后检测空腹血糖(FBG)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)及一氧化氮合酶(NOS)水平,检测AL-1和NDS对2型糖尿病大鼠胰岛形态学及胰岛素水平的影响。结果 AL-1能显著降低2型糖尿病大鼠FBG水平,其降糖作用及对胰岛形态的保护作用比NDS、穿心莲内酯(Andro)、硫辛酸(LA)及格列本脲(Gli)更好;并且AL-1可显著降低血清MDA水平,上调血清SOD和NOS水平。结论 AL-1对2型糖尿病大鼠的降血糖作用及对胰岛形态的保护作用比NDS更显著,结合AL-1与NDS的化学结构,推测二硫键是AL-1起疗效的活性部位之一;且AL-1可消除自由基,抗氧化应激作用是AL-1发挥抗糖尿病作用的机制之一。Objective To investigate the protective effect of AL-1 and NDS on rats with type 2 diabetes mellitus （DM）. Methods Type 2 DM in rats was induced by high-fat diets （HFD） and streptozotocin （STZ, ip, 35 mg·kg^-1）. FBG level was determined 1 week after the treatment. Serum superoxide dismutase （SOD）, serum malondialdehyde （MDA） and serum nitric oxide synthase （NOS） levels were measured to determine the changes of cellular antioxidant defense system. Hematoxylin-eosin staining and insulin immunohistochemistry were used to evaluate the rat pancreas. Results In HFD and STZ induced type 2 DM model rats, AL-1 lowered the FBG level. The effect of AL-1 was better than that of NDS, andrographolide （Andro） and alpha lipoic acid （LA）. AL-1 suppressed the level of serum MDA and improved contents of serum SOD and NOS. Conclusion AL-1 may lower the FBG level in type 2 DM rats. The effect of AL-1 is better than that of NDS. Compared with the chemical structure and protective activity of NDS, the disulfide bond is important for antidiabetic activity. AL-1 is effective in scavenging free radicals, which suggests that anti-oxidation is partially responsible for the effect ofAL-1. Key words： andrographolide; alpha lipoic acid; diabetes; antioxidant

关 键 词：穿心莲内酯 硫辛酸 糖尿病 抗氧化 

分 类 号：R965[医药卫生—药理学] R977.15[医药卫生—药学]