阿托伐他汀减轻兔血管损伤后再狭窄机制的研究

Atorvastatin Reduce Blood Vessel Restenosis After Injury in Rabbits

关键词:  阿托伐他汀  再狭窄  MMPs  PKC

Key words:  atorvastatin  restenosis  MMPs  PKC

摘要:

目的 观察阿托伐他汀对兔血管损伤后再狭窄的干预作用，探讨其与PKC、MMPs的关系。方法 将40 只健康日本大耳兔，♂，分为5组，每组8只，模型组及阿托伐他汀高(2 mg·d^-1)、中(1 mg·d^-1)、低(0.5 mg·d^-1)剂量组均行髂动脉二次损伤造模术，假手术组仅结扎股动脉。一月后取靶血管切片HE染色，图像分析仪检测各组内膜面积、中膜面积、管腔面积、内膜增生指数及狭窄指数；免疫组化检测各靶血管MMP-2、MMP-9、PKC表达。结果 经髂动脉二次损伤能成功建立血管成形术后再狭窄模型。与模型组相比，随剂量升高，阿托伐他汀各组内膜面积、中膜面积、膜增生指数及狭窄指数显著降低，管腔面积显著增加(P<0.01)，与此同时，靶血管MMP-2、MMP-9及PKC表达均显著降低，差异有统计学意义(P<0.01)。结论 阿托伐他汀能显著减轻兔血管成形术后再狭窄，其机制可能与通过PKC途径抑制靶血管MMPs表达有关。

Abstract:

OBJECTIVE To study the intervention role of atorvastatin in restenosis after angioplasty of iliac artery in rabbits, investigate its relationship with metalloproteinases(MMPs) and protein kinase C(PKC). METHODS All 40 white ♂ rabbits of Japan were randomly divided into 5 groups(n=8): model group; atorvastatin group with different doses of high (2 mg·d^-1), medium (1 mg·d^-1) and low (0.5 mg·d^-1) (iliac artery secondary injury); sham operation group (femoral artery ligation). HE dyeing was carried out in the target blood vessel after one month. Image pathology was used to analyse the intima area, tunica media area, vascular lumen area, index of intima hyperplasia and luminal stenosis. Immunohistochemical method was used to detect the expression of MMP-2, MMP-9 and PKC. RESULTS Iliac artery secondary injury could successfully bulid a restenosis model after angioplasty. Compared with model group, as the dosage increased, the atorvastatin groups had smaller intima area, tunica media area, index of intima hyperplasia and luminal stenosis, and there was a significant increase in the vascular lumen area(P<0.01), meanwhile, the expression of MMP-2, MMP-9 and PKC significantly reduced(P<0.01). CONCLUSION Atorvastatin can significantly reduce restenosis after rabbit angioplasty, the probable mechanism is through the way of PKC to inhibit the expression of MMPs in target blood vessels.