基质金属蛋白酶及其抑制剂在家兔血管成形术后血管重构中的作用

目的：探讨基质金属蛋白酶及其抑制剂（MMPs/TIMPs）在家兔血管成形术后血管重构中的作用及中药通心络的影响。 方法： （1）家兔65只分4组（对照组5只，拉伤组20只，高脂组20只，通心络组20只）采用高胆固醇（1.5 g·kg-1·d-1）喂养加两次腹主动脉损伤的方法制成动脉粥样硬化和血管成形术模型， X光下行血管成形术。术后分别治疗4周处死，取血管标本进行检测。（2）HE染色计算机图像分析血管形态的变化。（3）MMP2和TIMP1免疫组化分析，RT-PCR方法测定MMP2、TIMP1的mRNA表达量。 结果： （1）HE染色证实有动脉粥样硬化斑块形成，腹主动脉造影显示有管腔狭窄。（2）RT-PCR结果显示通心络组的MMP2和TIMP1 mRNA表达量低于高脂拉伤组P<0.05； MMP2和TIMP1比值更接近1。（3）免疫组化染色通心络组MMP2和TIMP1的阳性细胞吸光度(%)明显低于高脂拉伤组，P<0.05。（4）内膜面积通心络组低于高脂拉伤组P<0.05；而管腔面积高于高脂拉伤组P<0.05；并且管腔面积的增加与内膜面积的减少不相等。 结论： MMP2和TIMP1参与家兔血管成形术后的血管重构，通心络可以调整MMP2和TIMP1的比值。

Role of MMP2/TIMP1 in the vascular remodeling after angioplasty in rabbits

AIM: To discuss the effects of matric metalloproteinasez and tissue inhibitor 1 (MMP2/TIMP1) on the vascular remodeling after angioplasty and the regulatory effect of tongxinluo on it in rabbits. METHODS: 65 male white rabbits (2.5-3.5 kg; 6-8 months) were divided into 4 groups: control group (n=5, normal diet ), injury group (n=20, normal diet plus intimal injury), high-lipid group (n=20, high cholesterol diet plus intimal injury) and tongxinluo group (n=20, tongxinluo 0.5 mg·kg-1·d-1, 4 weeks, also high cholesterol diet plus intimal injury). Under X-ray the narrow parts of the vessel underwent angioplasty. All rabbits were killed and vessel samples were excised, respectively, for the detection of histomorphometry immunohistochemically and RT-PCR. The data were expressed as ±s. RESULTS: (1) The change of vascular morphological results showed that the intimal area in tongxinluo group was less than that in high-lipid group (P<0.05), inversely the lumen area in tongxinluo group was higher than that in high-lipid group (P<0.05). The difference between the increase in lumen area and the decrease in intimal area suggested that the vascular remodeling exist. (2) RT-PCR showed that the relative level of mRNA of MMP2 and TIMP1 in tongxinluo group was less than those in high-lipid group (P<0.05). (3) The immunohistochemical staining showed that the light absorption of MMP2 and TIMP1 in Tongxinluo group was less than that in high-lipid group (P<0.05). CONCLUSION: Tongxinluo inhibits the accumulation and secretion of extracellular matrix, also inhibits vascular remodeling in rabbits, which is related with MMP2 and TIMP1.