天津医药

• 实验研究 •    

丹酚酸B对糖尿病动脉粥样硬化ApoE基因敲除小鼠斑块面积及斑块内AGEs和RAGE表达的影响

郑纺1,范英昌2,姜希娟1,王宇春1   

  1. 1. 天津中医药大学
    2.
  • 收稿日期:2010-05-20 修回日期:2010-06-13 出版日期:2010-09-15 发布日期:2010-09-15
  • 通讯作者: 郑纺

Effects of Salvianolic Acid B on Atherosclerotic Plaque Area and Expressions of AGEs/RAGE in ApoE-Gene Knock-out Mice Treated with STZ and High Fat Diet

  • Received:2010-05-20 Revised:2010-06-13 Published:2010-09-15 Online:2010-09-15
  • Contact: ZHENG Fang

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摘要： 摘要 目的 观察丹酚酸B对高脂高糖联合介导下ApoE基因敲除小鼠（ApoE-/-）的动脉粥样硬化斑块面积和斑块内AGEs/RAGE表达水平的影响，以探讨丹酚酸B对抗糖尿病动脉粥样硬化的作用及可能的发生机制。方法 选取50只8周龄雌性ApoE-/-小鼠，腹腔注射链尿佐菌素200mg/kg联合高脂饲料喂养12周，将血糖水平>11.1mol/L的40只ApoE-/-小鼠作为糖尿病动脉粥样硬化模型小鼠，随机分为模型组（MOD）、丹酚酸B高剂量组（SalBH）、丹酚酸B中剂量组（SalBM）与洛伐他汀组（LVT）4组，每组10只。其中SalBH组灌服丹酚酸B 160mg/kg/d，SalBM灌服丹酚酸B 80mg/kg/d，LVT灌服洛伐他汀 2.3mg/kg/d，MOD组灌服等量蒸馏水，各组均连续灌胃8周。实验期满后，取全部小鼠血样，测定空腹血糖水平；取小鼠主动脉，制备石蜡或冰冻切片，分别进行HE染色和免疫组化染色或苏丹Ⅲ染色，观察动脉粥样硬化斑块面积及斑块内AGEs和RAGE的表达情况，利用Image-Pro Plus Version 6.0(IPP)图像分析系统计算结果。结果 各治疗组与MOD组比较斑块面积和校正斑块面积明显降低（P＜0.05）；各治疗组间比较斑块面积和校正斑块面积差异也有统计学意义（P＜0.05），其中LVT组最低，SalBH组稍高，SalBM组最高。各治疗组与MOD组比较，AGEs平均光密度明显降低（P＜0.05），而RAGE平均光密度值无差异（P＞0.05）；各治疗组间AGEs和RAGE的平均光密度差异无统计学意义（P＞0.05）。结论 丹酚酸B能够减少糖尿病动脉粥样斑块面积，该作用可能是通过降低斑块内AGEs的表达来实现的。

关键词: 丹酚酸B, ApoE-/-, 斑块面积, 晚期糖基化终末产物, RAGE

Abstract: Abstract Objective To observe the effects of Salvianolic acid B(SalB) on plaque area and AGEs/RAGE expression of plaque in diabetic atherosclerosis animal models prepared from apolipoprotein E(ApoE) gene knock-out mice treated by intraperitoneal injection of STZ and high fat diet. Methods Fifty two-month female ApoE gene knock-out mice were injected with STZ and fed with high fat diet for 12 months. Then blood sugar level was measured and forty diabetic atherosclerosis mice were selected for the following treatment experiment. Diabetic atherosclerosis mice were randomly divided into four groups. Each group was fed with same high fat diet and intragastrically administrated with different drugs for 8 weeks, named MOD group(distilled water)、SalBH(SalB 160mg/kg/d) group、SalBM group(SalB 80mg/kg/d) and Lovastatin（LVT 2.3mg/kg/d）group. Then fasting blood sugar level(FBG) was measured by using full automatic biochemistry instrument. Frozen sections and paraffin sections of mice aortas were made. The plague area、plaque area corrected by cross-sectional vessel wall area as well as the expressions of AGEs and RAGE were measured by Sudan Ⅲstaining or HE staining and immunohistochemistry staining and then analyzed by Image-Pro Plus(IPP) version 6.0 system. Results Compared with the MOD group, plaque area reduced significantly in SalBH、SalBM and LVT treatment group（P＜0.05）;besides plaque area of LVT group is lower than that of SalBH group and plaque area of SalBH group is lower than that of SalBM（P＜0.05）. Compared with the MOD group, average optical density value of AGEs reduced significantly in SalBH、SalBM and LVT treatment group（P＜0.05）. Conclusions SalB can reduce the diabetic atherosclerotic plaque area by decreasing the expressions of AGEs and RAGE in atheromatous plaque.

Key words: Salvianolic acid B Apolipoprotein E-gene knock-out mice plaque area Advanced Glycation Endoproducts（AGEs） RAGE