CyPA及p-ERK1/2在动脉粥样硬化大鼠血管内皮中的表达

Expression of CyPA and p-ERK1/2 in atherosclerosis lesion of rats with atherosclerosis disease

目的观察动脉粥样硬化(AS)大鼠血管内皮功能以及亲环素A(Cy PA)和磷酸化细胞外信号调节激酶1/2(pERK1/2)的表达变化。方法将30只雄性Wistar大鼠随机分为3组(每组10只):对照组、AS 12周组,AS 16周组。对照组给予基础饲料喂养+腹腔注射等量生理盐水;AS组给予高脂饲料喂养+维生素D3注射液60万IU/kg一次性腹腔注射。对应不同造模时间处死大鼠,分离腹主动脉,观测离体腹主动脉环对乙酰胆碱的舒张反应;HE染色、免疫组化法检测动脉血管壁Cy PA及p-ERK1/2的表达。结果与对照组比较,AS 12周、AS 16周组血管内皮功能下降,3组差异有统计学意义(P<0.05);HE染色显示对照组大鼠血管壁呈正常结构,AS 12周组大鼠内皮细胞破坏、平滑肌细胞增生,AS 16周组粥样钙化斑块形成;免疫组化分析显示3组大鼠血管壁内Cy PA及p-ERK1/2表达逐渐升高,差异有统计学意义(P<0.05)。结论随着AS程度加重,大鼠血管内皮依赖性舒张功能明显下降,动脉粥样钙化斑块严重,Cy PA及p-ERK1/2表达显著增加。Cy PA、p-ERK1/2信号机制参与加重血管动脉粥样硬化进展,可能是促进AS进展的途径之一。

Objective To observe the change of endothelial-dependent vasodilatation and the expression of cyclophilin A（ Cy PA） and phosphorylated extracellular signal regulated kinase 1/2（ p-ERK1/2） in atherosclerosis lesion of high cholesterol diet fed rats. Methods Thirty male wistar rats were randomly divided into three groups： the control group,AS 12 W group and AS 16 W group. The rats in the control group were fed with base diet. The rats in AS groups were fed with high cholesterol diet and given intraperitoneal injection of a single dose of Vitamin D3 600000 IU/kg. The rats were excuted after 16 weeks,the response of the separated aorta abdominalises to acethylcholine was examined in ex vivo organ bath. Besides,the aorta abdominalises were stained with hematoxylin and eosin,and the expression of Cy PA and p-ERK1/2 was detected by immunohistochemical staining. Results Compared with the control group,it obviously declined in endothelial-dependent vasodilatation of the AS 12 W group and AS16 W group,the differences of three groups had statistical significance（ P〈0. 05）. HE staining showed that normal vessel structure was observed in the control group,endothelial cells damage and vessel smooth muscle cells proliferation was observed in AS 12 W group,formation of atheromatous plaque and calcified plaque was observed in AS16 W group. Immunohistochemical analysis suggested that the expression of Cy PA and p-ERK1/2 were increasing in AS groups. Moreover,the differences of three groups had statistical significance（ P〈0. 05）. Conclusion Cy PA and p-ERK1/2 may be one of mechanisms to promote the progress of atherosclerosis.