心脑血脉宁对家兔动脉粥样硬化易损斑块模型MMP-2、TIMP-2表达的影响

Expression of MMP-2,TIMP-2 of vulnerable plaque in rabbits with atherosclerosis treated with Xinnao Xuemaining

[目的]探讨心脑血脉宁对家兔动脉粥样硬化易损斑块模型基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响。[方法]通过喂养高脂饲料和主动脉球囊内皮拉伤术复制动脉粥样硬化易损斑块模型,实验分为模型组,假手术组,心脑血脉宁组,历时15周。处死后,取腹主动脉行苏木精-伊红(HE)染色,观察镜下病变,计数斑块破裂数,免疫组化方法检测MMP-2、TIMP-2蛋白含量。[结果]1)HE观察:假手术组镜下形态结构完整,模型组斑块中心可见大量脂核,斑块表面覆盖纤维帽,在斑块肩部可见残存泡沫细胞和大炎细胞浸润。心脑血脉宁组介于两者之间。2)免疫组化结果:与假手术组相比,模型组MMP-2、TIMP-2蛋白含量明显升高,差异有显著性(P<0.01);心脑血脉宁组MMP-2与模型组比较表达降低,差异有显著性(P<0.01),而TIMP-2含量与模型组相比有降低趋势,但无统计学差异(P>0.05);心脑血脉宁组能够有效降低两者比值,与模型组相比差异有显著性(P<0.01)。[结论]心脑血脉宁干预家兔动脉粥样硬化易损斑块模型,能减少斑块破裂,其机制可能与降低斑块MMP-2含量以及调节MMP-2与TIMP-2比值有关。

[ObjectiVe] To observe the effects of Xinnao Xuemaining on the expression of MMP-2, TIMP-2 of vulnerable plaque in rabbits with atherosclerosis. [Methods] The vulnerable atherosclerotic plaque model was reproduced by operation on abdominal aorta endotheli- um for inducing sacculus pull injury with the foraging with high cholesterol lipid feeding. Rats were divided into three groups： model group, sham operation group and Xinnao Xuemaining group. The experiment lasted for 15 weeks. After killing at the end of experiment, the sample of abdominal aorta was collected for HE staining and microscopic lesion examination, counting of the number of plaque rup- ture and detecting the protein content of MMP-2, TIMP-2 by immunohistochemistry. [Results] HE observation was found that in the sham-operated group the morphologic structure was intact. In the center of model group a large number of lipid plaque cores was seen. The plaque was covered with fibrous cap, the shoulder patches were visible in the remnants of foam cells and large inflammatory cell in- filtration exited. In Xinnao Xuemaining group the number of lipid plaque cores was between model and sham operation group. The results of immunohistochemical staining showed that compared with sham-operated group, the expression of MMP-2, TIMP-2 in model group was significantly increased （P〈0.01）. Compared with model group the expression of MMP-2 in Xinnao Xuemaining group reduced significantly （P〈0.01）. The TIMP-2 levels wee lower, but there was no statistical difference （P〉0.05）. Xinnao Xuemaining group can effectively reduce both the ratio of MMP-2/TIMP-2 compared with model group （P〈0.01）. [Conclusion] In vulnerable plaque of atherosclerotic rabbit model Xinnao Xuemaining group can reduce the plaque rupture, its mechanism may be related to reducing the expression of MMP-2 and regulat- ing the ratio of MMP-2 and TIMP-2.