摘要
目的观察左归复方(滋阴益气活血解毒组方)干预治疗MKR小鼠后,糖代谢及PPARγ在肝脏、骨骼肌和脂肪组织中的表达变化。方法取MKR小鼠40只,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(阳性药对照组),每组10只,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30d。末次给药后0.5h,空腹测定血糖;心脏取血,放射免疫法测定血清胰岛素,RT-PCR法检测PPARγmRNA在肝脏、骨骼肌中的表达,Western Blotting及免疫组化法检测PPARγ蛋白在肝脏、骨骼肌和脂肪组织中的表达。结果左归复方干预治疗后,其高剂量组具有显著的降低MKR小鼠空腹血糖、改善高胰岛素血症的作用(P<0.05或P<0.01)。与C57野生鼠组比较,MKR模型组小鼠肝脏和骨骼肌PPARγmRNA表达均显著下调(P<0.01),而其蛋白表达在骨骼肌和脂肪组织中也显著下调(P<0.05);经左归复方治疗后,与MKR模型组比较,左归复方高剂量组MKR鼠肝脏和骨骼肌PPARγmRNA表达均明显上调(P<0.05),PPARγ蛋白表达在三种组织中均显著上调(P<0.05或P<0.01)。左归复方上调各组织中PPARγmRNA及蛋白表达与阳性对照药文迪雅组作用相当(P>0.05)。结论左归复方具有显著的改善MKR鼠糖代谢的作用,其机制与上调肝脏、骨骼肌和脂肪组织中PPARγ表达,增强外周组织对胰岛素的敏感性,改善胰岛素抵抗有关。
Objective To observe the effect of of Zuogui Recipe (ZR) on glucose metabolism and PPARγ expression in the liver, skeletal muscle and fat 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) level and the serum insulin level were determined; the expression of PPARγ mRNA in the liver and skeletal muscle was determined by RT - PCR and the expression of PPAR~ protein in the liver, skeletal muscle and fat tissue was determined by Western Blotting and SABC immunohistochemistry. Results After treatment, hyperglycemia in HZP was significantly ameliorated and fasting blood glucose was decreased ( p 〈 0. 05 or P 〈 0. 01 ). Comparing with C57 mice, the expression of PPAR~ mRNA were decreased in the liver and skeletal muscle of model group ( P 〈 0. 01 ), and the expression of PPARγ protein were also decreased in the skeletal muscle and fat tissue ( P 〈 0. 05). After treatment, the expression of PPARγ mRNA in the liver and skeletal muscle of HZP group and that of PPARγ mRNA in the liver, skeletal muscle and fatty tissue were significantly increased ( p 〈 0. 05 or P 〈 0.01 compared with the model group). The up - regulation of PPARγ mRNA and protein expression of ZP was similar to that of rosiglitazone maleate. Conclusion ZP has obvious effect on improving glucose metabolism in MKR mice, and its mechanism may be related to the increase of PPAR3' expression in liver, skeletal muscle and fat tissue, the in- crease of sensitivity of peripheral tissue to insulin, and the improvement of insulin resistance in the mice.
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2009年第2期111-115,共5页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金(30400604)
国家中医药管理局回国留学人员项目(国中医药发[2004]68号-1)
湖南省教育厅优秀青年基金(07B055)
湖南省自然科学杰出青年基金(08JJ1005)
湖南省教育厅一般项目(08C620)
关键词
左归复方
滋阴益气
2型糖尿病
MKR鼠
PPARΓ
Zuogui recipe
Nourishing Yin and invigorating Qi
Type 2 diabetes mellitus
MKR mice
PPARγ