丹酚酸B对糖尿病动脉粥样硬化斑块内血栓相关因子的影响

Effects of salvianolic acid B on expression of tissue factor and plasminogen activator inhibitor-1 in ApoE-gene knock-out mice treated with STZ and high fat diet

关键词:  丹酚酸B  载脂蛋白E基因敲除小鼠  组织因子I  型纤溶酶原激活物抑制剂

Key words:  salvianolic acid B  apolipoprotein E-gene knock-out mice  tissue factor plasminogen activator inhibitor-1

摘要:

[目的]观察丹酚酸B对抗糖尿病动脉粥样硬化斑块血栓形成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200 mg/kg联合高脂饲料喂养12周,将血糖水平>11.1 mol/L 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。各组均连续灌胃8周。实验期满后,测定空腹血糖水平;酶联免疫吸附(ELISA)法检测血清I型纤溶酶原激活物抑制剂(PAI-1)的浓度。免疫组织化学染色检测斑块内组织因子(TF)的表达,利用Image-Pro Plus Version 6.0(IPP)图像分析系统计算结果。[结果]与MOD组比较,各治疗组TF平均光密度值明显降低(P<0.05);与MOD组比较,SalBM组PAI-1浓度明显降低(P<0.05)。[结论]丹酚酸B能够降低糖尿病动脉粥样硬化斑块内TF的表达和血清PAI-1含量,提示丹酚酸B可能是通过以上机制来减少粥样硬化斑块内的血栓形成。

Abstract:

[Objective] To observe the effect of Salvianolic acid B on thrombogenesis of atheromatous plaque in mice with diabetic atherosclerosis and the possible mechanism.[Methods] Fifty two-month female ApoE-gene knock-out mice were intraperitoneally inject-ed with 200 mg/kg 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 and the mice in each group were fed with same high fat diet and administrated per oral with different drugs for 8 weeks,named MOD group(dis-tilled water),SalBH [SalB 160 mg/(kg·d)] group,SalBM group[SalB 80 mg/(kg·d)] and Lovastatin[LVT 2.3 mg/(kg·d)] group.Then fast blood sugar level(FBG) was measured by using full automatic biochemistry instrument;the concentration of blood plasminogen activator inhibitor-1(PAI-1)was determined by ELISA techniques.Mice aortas were subjected to fixation and paraffin imbedding,then paraffin sections were made.The expression of tissue factor(TF)was measured by immunohistochemistry staining and then analyzed by Image-Pro Plus(IPP) version 6.0 system.[Results] Compared with the MOD group,average optical density(OD) value of TF reduced significantly in SalBH,SalBM and LVT treatment group(P<0.05);PAI-1 concentration reduced significantly in SalBM group(P<0.05).[Conclusions] Salvianolic Acid B can decrease the expression of TF in atheromatous plaque and concentration of blood PAI-1.The result suggested that Salvianolic Acid B may reduce thrombogenesis by above mechanism.