丹酚酸B对高脂高糖联合介导的载脂蛋白E基因敲除小鼠动脉粥样硬化斑块稳定性的影响

Effects of Salvianolic Acid B on Stability of Atherosclerotic Plaque in Apolipoprotein E Gene Knock-out Mice Treated with STZ and High Fat Diet

目的观察丹酚酸B对高脂高糖联合介导的载脂蛋白E基因敲除小鼠动脉粥样硬化斑块稳定性的影响及可能的发生机制。方法选取50只8周龄雌性载脂蛋白E基因敲除小鼠,腹腔注射链脲佐菌素200 mg/kg联合高脂饲料喂养12周,将血糖水平>11.1 mol/L的40只载脂蛋白E基因敲除小鼠随机分为模型组、丹酚酸B高剂量组、丹酚酸B中剂量组和洛伐他汀组,每组10只。其中丹酚酸B高剂量组灌服丹酚酸B 160 mg/(kg.d),丹酚酸B中剂量组灌服丹酚酸B 80 mg/(kg.d),洛伐他汀组灌服洛伐他汀2.3 mg/(kg.d),模型组灌服等量蒸馏水,连续灌胃8周。实验期满后,取小鼠血样测空腹血糖和血脂水平;取小鼠主动脉,分别制备主动脉冰冻切片和石蜡包埋切片,进行苏丹Ⅲ染色、MASSON染色和免疫荧光化学染色,观察斑块内脂质中心面积和纤维帽厚度及斑块糜烂发生率和斑块内新生血管数目。结果丹酚酸B高剂量组、洛伐他汀组与模型组比较空腹血糖和总胆固醇水平明显降低(P<0.05);丹酚酸B中剂量组、高剂量组及洛伐他汀组与模型组比较甘油三酯和低密度脂蛋白胆固醇水平明显降低(P<0.05),而高密度脂蛋白胆固醇水平明显升高(P<0.05)。丹酚酸B中剂量组、高剂量组与模型组比较脂质中心面积占斑块面积百分比、斑块内新生血管数目及斑块糜烂发生率明显降低(P<0.01),纤维帽平均厚度明显增高(P<0.01)。结论丹酚酸B能够提高糖尿病动脉粥样硬化斑块的稳定性,该作用可能是通过增加平均纤维帽厚度,降低斑块内脂质含量、斑块糜烂发生率和斑块内血管新生等方式来实现的。

Aim To observe the effect of Salvianolic acid B（SalB） on atherosclerotic plaque stabilization 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 weeks.Then fasting blood glucose（FBG） 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 model group（distilled water）,SalB high dose group（160 mg/（kg·d））,SalB medium dose group（80mg/（kg·d）） and Lovastatin group（2.3 mg/（kg·d））.Then frozen sections and paraffin sections of mice aortas were made.The lipid core area,thickness of fibrous cap,incidence of plaque erosion and the number of neovascularization in atheromatous plaque were measured by Sudan III staining,MASSON staining and immunohistochemistry staining. Results Compared with the model group,both the level of FBG and total cholesterol（TC） in the SalB high dose group and Lovastatin group reduced significantly（P0.05）.Compared with the model group,both the level of triglyceride（TG） and low density lipoprotein cholesterol（LDLC） in the SalB medium dose group,SalB high dose group and Lovastatin group reduced significantly（P0.05）,whereas the level of high density lipoprotein cholesterol（HDLC） increased significantly（P0.05）.Compared with the model group,lipid core area,the number of neovascularization in atheromatous plaque and the incidence of plaque erosion in the SalB medium dose group,SalB high dose group reduced significantly（P0.01）,whereas average thickness of fibrous cap became thicker significantly（P0.01）.Conclusions SalB may stabilize the diabetic atherosclerotic plaques by increasing average thickness of fibrous cap and decreasing lipid core area,incidence of plaque erosion and neovascularization in atheromatous plaque.