p38和丝裂原活化蛋白激酶磷酸酶1在内膜损伤后血管平滑肌细胞表型转化过程中的表达变化  

Changes of p38 and Mitogen-Activated Protein Kinase Phosphatase-1 in Phenotypic Modulation of Vascular Smooth Muscle Cells After Intimal Injury

作　　者：张新平[1] 庞月华 冯义伯[1] 付作林[1] 史春志[1] 谷翔[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心内科,湖北省武汉市430022 [2]乌鲁木齐市友谊医院,新疆维吾尔自治区乌鲁木齐市830049

出　　处：《中国动脉硬化杂志》2006年第2期127-131,共5页Chinese Journal of Arteriosclerosis

摘　　要：目的观察动脉内膜损伤后血管平滑肌细胞表型转化和p38及丝裂原活化蛋白激酶磷酸酶1表达的动态变化。方法分别用免疫组织化学、免疫印迹和逆转录聚合酶链反应方法检测假损伤组和损伤后不同时间点血管壁中增殖细胞核抗原、平滑肌a肌动蛋白、p38蛋白和丝裂原活化蛋白激酶磷酸酶1蛋白及其mRNA的表达。结果假损伤组血管中膜平滑肌细胞及内皮细胞增殖细胞核抗原为阴性表达；损伤后5～14天，新生内膜阳性细胞率逐渐增加．28天后开始逐渐减少，且新生内膜阳性率均略高于中膜。假损伤组血管中膜平滑肌a肌动蛋白表达为阳性，内皮为阴性：中膜阳性面积于损伤后1天开始减少，3天最为明显，5天后开始逐渐增加，且新生内膜阳性表达略低于中膜。假损伤组血管中膜p38呈阴性或弱阳性着色；损伤后1～35天呈持续高表达，新生内膜阳性表达高于中膜。p38表达变化与增殖细胞核抗原表达变化呈正相关。假损伤组血管中膜丝裂原活化蛋白激酶磷酸酶1呈弱阳性或阳性表达；损伤后1天即开始下降，14-28天稍有回升，至35天仍未回到假损伤组水平，且新生内膜阳性面积稍低于中膜。其表达变化与增殖细胞核抗原表达变化呈负相关。结论内膜损伤后血管平滑肌细胞增殖能力与其表型转化密切相关，p38和丝裂原活化蛋白激酶磷酸酶1参与了损伤后血管平滑肌细胞表型转化的信号转导及调节。Aim To explore phenotypic modulation of vascular smooth muscle cells （VSMC） and change of p38, mitogen-activated protein kinase phosphatase-1 （MKP-1） expression after intimal injury. Methods The model of vascular restenosis established by intimal injury of rabbit carotid arteries was used. Immunohistochemistry, Western blot and reverse transcriptase-polymerase chain reaction （RT-PCR） were used to detect the changes of proliferation cell nuclear antigen （PCNA）, smooth muscle a-actin （SM a-actin）, p38 protein, and MKP-1 protein as well as its mRNA of sham-injured arteries and injured arteries at different time points. Results PCNA was negative in the medium and endothelium in sham-injured arteries. Positive cell rate of PCNA was gradually increased at 1 - 14 days in the medium and at 5 - 14 days in the neointima after injury, but it declined gradually after 28 days. Positive cell rate of PCNA in the neointima was shghfly more than that in the medium at different time points. SM a-actin was positive in the medium, negative in the endothehum in sham-injured arteries. SM a-actin initially decreased in the medium at 1 day, it was minimal at 3 days after injury, but it increased gradually after 5 days. Positive expression of SM a-actin in the neointima was slightly lower than that in the medium, p38 was negative or feeble positive in the medium in sham-injured arteries, p38 was continuously increased at 1 - 35 days after injury. Positive expression of p38 in the neointima was higher than that in the medium. There was positive relationship between change of p38 and that of PCNA in the vascular wall at different time points after injury. MKP-1 was feeble positive or positive in sham-injured arteries. MKP-1 initially decreased at 1 day and increased graduallv from 14 - 28th day, but it was still lower than that in the sham-injured arteries on 35th day after injury. There was negative relationship between change of MKP-1 and that of PCNA in the vascular wall at different time points after injury. Conclus

关 键 词：病理学与病理生理学 p38和丝裂原活化蛋白激酶磷酸酶1与内膜增殖相关 免疫组织化学染色 丝裂原活化蛋白激酶磷酸酶1 内膜损伤 血管平滑肌细胞 P38 

分 类 号：R363[医药卫生—病理学]