MKR转基因2型糖尿病小鼠脂肪组织p38丝裂原活化蛋白激酶、c-jun氨基末端激酶蛋白的表达及左归复方的保护作用
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国家自然科学基金项目(30973749);;湖南省自然科学基金杰出青年基金(08JJ1005);;湖南省中医药科研基金重点项目(2009003);;湖南省高校创新平台开放基金(09K059)


Research on p38 Mitogen-activated Protein Kinase and c-jun Amino-terminal Kinase Expression in Adipose Tissue of Transgenic Type 2 Diabetic MKR Mice and Protective Action of Zuogui Recipe
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    目的观察MKR转基因2型糖尿病小鼠脂肪组织磷酸化p38丝裂原活化蛋白激酶、c-jun氨基末端激酶蛋白表达的变化及左归复方(滋阴益气活血解毒组方)的保护作用。方法40只MKR小鼠经鉴定后,随机分为MKR模型组、左归复方高、低剂量组、文迪雅组,每组10只。C57BL/6J(C57)野生鼠10只作为空白对照组。各药物组分别以相应剂量连续给药30天。于给药前、第15天及第30天,分别作空腹血糖测定。末次给药后0.5 h,心脏取血,放射免疫法测血清胰岛素,酶联免疫吸附测定法检测血清细胞间黏附分子、血管细胞黏附分子,Westernblotting和免疫组织化学检测磷酸化p38丝裂原活化蛋白激酶、c-jun氨基末端激酶蛋白在脂肪组织中的表达。结果①左归复方干预治疗后,其高剂量具有显著的降低MKR小鼠空腹血糖、改善高胰岛素血症的作用(P<0.05,P<0.01);②MKR鼠具有显著增高的炎症因子水平,而左归复方干预治疗后具有降低与炎症反应相关的细胞间黏附分子1和血管细胞黏附分子1水平的作用(P<0.01);③MKR小鼠脂肪组织中p38丝裂原活化蛋白激酶和c-jun氨基末端激酶蛋白表达均上调,但与C57野生鼠比较差异无统计学意义(P>0.05);左归复方干预治疗后,MKR小鼠脂肪组织中p38丝裂原活化蛋白激酶和c-jun氨基末端激酶蛋白表达均显著下调(P<0.05,P<0.01),左归复方下调p38丝裂原活化蛋白激酶和c-jun氨基末端激酶蛋白表达与阳性对照药文迪雅作用相当。结论左归复方能显著改善MKR小鼠糖代谢及其炎症损伤,其机制为下调脂肪组织中磷酸化p38丝裂原活化蛋白激酶和c-jun氨基末端激酶蛋白表达,增强脂肪组织对胰岛素的敏感性和炎症抑制作用。

    Abstract:

    Aim To observe the effect of of Zuogui recipe(ZR) on glucose metabolism and p38 mitogen-activated protein kinase(p38MAPK) and c-jun amino-terminal kinase(JNK) expression in the adipose tissue of MKR mice.Methods Forty qualified MKR mice were equally randomized into 4 groups:model group(MG),low-dose ZP group(LZP),high-dose ZP group(HZP) and positive control group(PCG).LZP,HZP and PCG were treated by corresponding drugs for 30 days.Using C57 mice as the controls,the fasting blood glucose(FBG),the serum insulin,and the serum intercellular cell adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) level were determined;the expression of p38MAPK and JNK protein in the adipose tissue were determined by Western blotting and the SABC im-munohistochemistry.Results Hyperglycemia in HZP was significantly ameliorated and fasting blood glucose was decreased after treatment(P<0.05 or P<0.01).Compared with C57 mice,the serum ICAM-1 and VCAM-1 level were significantly increased,and the expression of p38MAPK and JNK protein in the adipose tissue of model group were increased weakly.After treatment,the serum ICAM-1 and VCAM-1 level were significantly decreased,and the expression of p38MAPK and JNK protein in the adipose tissue of HZP and LZP groups were also significantly decreased(P<0.01),compared with the model group.Conclusion Zuogui recipe has obvious effect on improving glucose metabolism and inflammatory reaction in MKR mice,and its mechanism may be related to the decrease of p38MAPK and JNK protein expression in adipose tissue,the increase of sensitivity of peripheral tissue to insulin,and the improvement of insulin resistance in the mice.

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吴勇军, 喻 嵘, 成细华, 夏金华, 吴 慧. MKR转基因2型糖尿病小鼠脂肪组织p38丝裂原活化蛋白激酶、c-jun氨基末端激酶蛋白的表达及左归复方的保护作用[J].中国动脉硬化杂志,2011,19(7):547~551.

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  • 收稿日期:2011-04-07
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