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二甲双胍对糖尿病大鼠脂肪组织AMPKα2及氧化应激水平的影响
宋玉萍,韩冲,史婧丽,吴莹,刘志民*
0
(第二军医大学长征医院内分泌科,上海 200003
*通信作者)
摘要:
目的 观察二甲双胍对2型糖尿病大鼠脂肪组织中腺苷酸活化蛋白激酶α2(AMPKα2)表达及对氧化应激水平的影响,探讨其改善血糖、氧化应激及胰岛素抵抗的可能机制。方法 32只雄性SD大鼠随机分为正常对照组(NC,n=12)、糖尿病模型组(DM,n=10)、二甲双胍治疗组(MT,n=10);后两组高脂饮食1个月后腹腔注射链脲佐菌素(STZ)30 mg/kg制备2型糖尿病大鼠模型。造模成功后,MT 组给予二甲双胍50 mg/(kg·d) 灌胃,NC组 、DM组给予同剂量0.5%羟甲基纤维素钠溶液。测定大鼠治疗前后的体质量,并检测各组空腹血糖(FBG)、空腹胰岛素(FINS)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、β-N-乙酰氨基葡萄糖苷酶(NAG)、髓过氧化物酶(MPO)、丙二醛(MDA)、单胺氧化酶(MAO)、总胆固醇(TC)、 三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平,计算大鼠脂体比、胰岛素敏感指数(ISI)。同时以半定量RT-PCR检测脂肪组织AMPKα2 mRNA的表达。结果 与DM组比较,MT 组脂肪组织AMPKα2 mRNA的表达及血清GSH、SOD、ISI、HDL增高, FINS、FBG、NAG、MDA、MPO、MAO、TC、TG、LDL降低, 差异均有统计学意义(P<0.05)。结论 二甲双胍调节2型糖尿病大鼠,糖脂代谢,改善胰岛素敏感性及氧化应激可能与脂肪组织AMPKα2的表达增加有关。
关键词:  二甲双胍  腺苷酸活化蛋白激酶α2  氧化性应激  2型糖尿病
DOI:10.3724/SP.J.1008.2012.00621
投稿时间:2011-11-10修订日期:2011-12-15
基金项目:
Influence of metformin on adipose AMPKα2 expression and oxidative stress level in diabetic rats
SONG Yu-ping,HAN Chong,SHI Jing-li,WU Ying,LIU Zhi-min*
(Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author.)
Abstract:
Objective To investigate the influence of metformin on AMP-activated Protein Kinaseα2 (AMPK α2) expression in adipose tissue and oxidative stress indices in diabetic rats, so as to understand the possible mechanism of metformin in improving blood glucose control, oxidative stress and insulin-resistance. Methods Totally 32 male SD rats were randomly divided into normal control (NC) group (n=12), model (T2DM) group (n=10) and metformin group (n=10). Rat model of T2DM was established by high fat/high glucose diet (one month) and intraperitoneal injection of streptozotocin (30 mg/kg). Animals in the metformin group were given 50 mg/(kg·d)( i.g.), and those in the other two groups were given same dose of 0.5% HPMC solution. The body masses of rats were determined before and after treatment. The fasting blood glucose (FBG), fasting insulin (FINS), superoxide dismutase (SOD), glutathione (GSH), N-acetyl-beta-D-glucosaminidase (NAG), malonaldehyde (MDA), myeloperoxidase (MPO), monoamine oxidase (MAO), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) levels were measured by ELISA and Biochemical Analyzer; the ratio of fat to body weight and insulin sensitivity index (ISI) were calculated. RT-PCR was used to evaluate the expression of AMPK α2 mRNA in the adipose tissues. Results Compared with DM group, metformin group had significantly higher AMPK α2 mRNA expression, serum GSH, SOD, ISI and HDL, and significantly lower serum FINS, FBG, NAG, MDA, MPO, MAO, TC, TG and LDL (P<0.05). ConclusionMetformin can increase AMPK α2 expression in the adipose tissue of diabetic rats, regulate glucose metabolism, and improve insulin sensitivity and oxidative stress.
Key words:  metformin  adenosine acid amp-activated protein kinase α2  oxidative stress