四妙勇安汤对动脉粥样硬化小鼠动脉血管斑块外膜滋养血管通透性的影响

目的:观察四妙勇安汤对动脉粥样硬化(atherosclerosis,AS)易损斑块病理形态及外膜滋养血管(vasa vasorum,VV)通透性的影响,并以VV为靶点探讨其干预机制。方法:采用健康雄性Apo E~(-/-)小鼠,随机分为模型组、四妙勇安汤组(11.7 mg·kg~(-1)·d~(-1))和辛伐他汀组(2.6 mg·kg~(-1)·d~(-1)),给予添加1.1%L-蛋氨酸的高脂饲料喂养;以C57BL/6小鼠作为正常组,喂养8周后进行模型评价,在模型成功基础上,持续药物干预8周,采用油红O染色观察小鼠主动脉的病理形态变化;通过免疫组化染色观察主动脉根部斑块外膜基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9),基质金属蛋白酶组织抑制因子-1(tissue inhibitor of metalloproteinase-1,TIMP-1)蛋白的表达情况。结果:油红O染色结果显示,与正常组比较,模型组主动脉血管内壁斑块面积显著增加(P0.01);与模型组比较,辛伐他汀组主动脉内壁斑块面积显著减少(P0.01);四妙勇安汤组主动脉内壁斑块面积明显减少(P0.05)。免疫组化染色结果显示,与正常组比较,模型组小鼠主动脉外膜MMP-9阳性表达面积明显增大(P0.01);与模型组比较,辛伐他汀组与四妙勇安汤组MMP-9阳性表达明显减小(P0.01);与辛伐他汀组比较,四妙勇安汤组MMP-9阳性表达明显减小(P0.01)。结论:四妙勇安汤能减轻小鼠主动脉斑块面积,通过调节MMP-9,TIMP-1的表达,降低斑块外膜VV通透性,稳定易损斑块。

Effect of Simiao Yongan Tang on Permeability of Vasa Vasorum of Atherosclerotic Plaque

Objective:To observe the effect of Simiao Yongan Tang on the pathologic morphology of atherosclerosis (AS) vulnerable plaque and the permeability of vasa vasorum (VV), and to explore its intervention mechanism with VV as the target. Method:Healthy male ApoE^-/- mice were randomly divided into model group, Simiao Yongan Tang group(11.7 mg·kg^-1·d^-1)and simvastatin group(2.6 mg·kg^-1·d^-1). High-fat diet supplemented with 1.1% L-methionine was given to induce the animal model, while C57BL/6 mice were used as the control group. The model was evaluated after 8 weeks of feeding. After successful modeling, continued drug intervention was given for 8 weeks, and the pathological changes of the mouse aorta were observed by oil red O staining. The expression levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins in the outer membrane of aortic root plaques were observed by immunohistochemical staining. Result:The results of oil red O staining showed that as compared with the control group, the plaque area of the aortic wall was significantly increased in the model group (P<0.01). As compared with the model group, the plaque area of the aorta was significantly decreased in the simvastatin group (P<0.01), end the area of plaque in the aortic wall was reduced in Simiao Yongan Tang group (P<0.05). The results of immunohistochemical staining showed that as compared with the normal control group, the positive expression of MMP-9 in the aortic adventitia was significantly increased in the model group (P<0.01). As compared with the model group, the positive expression of MMP-9 was significantly decreased in simvastatin group and Simiao Yongan Tang group(P<0.01). As compared with the simvastatin group, the positive expression of MMP-9 was significantly decreased in Simiao Yongan Tang group (P<0.01). Conclusion:Simiao Yongan Tang can reduce the area of mouse aortic plaque, reduce the VV permeability of the outer plaque by regulating the expression of MMP-9 and TIMP-1, and stabilize the vulnerable plaque.