动脉内膜损伤后血管平滑肌细胞表型转化及MKP-1表达的变化  

Phenotypic modulation of vascular smooth muscle cells and change of mitogen-activated protein kinase phosphatase-1(MKP-1) after intimal injury

作　　者：张新平[1] 庞月华 冯义伯[1] 谷翔[1] 黎明[1] 付作林[1] 史春志[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,湖北武汉430022 [2]乌鲁木齐市友谊医院,新疆乌鲁木齐830049

出　　处：《心脏杂志》2005年第6期524-527,541,共5页Chinese Heart Journal

摘　　要：目的:观察动脉内膜损伤后血管平滑肌细胞(vascular smooth muscle cells,VSMC)表型转化和丝裂原激活蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1,MKP-1)表达的动态变化.方法:分别用HE染色、免疫组化和逆转录-聚合酶链(RT-PCR)方法检测假损伤组(S组)和损伤后不同时间点血管形态学改变及血管壁中增殖细胞核抗原(PCNA)、平滑肌α肌动蛋白(SMα-actin)和MKP-1 mRNA及蛋白表达的变化.结果:①损伤后1 d中膜腔侧、3 d管腔内表面可见增殖的VSMC,5～7 d新生内膜(neointima,NI)形成并逐渐增厚,14～35 d NI进行性增厚;各组中膜均有增殖的VSMC向腔面集聚.②S组中膜VSMC及内皮细胞PCNA为阴性;中膜于损伤后1～14d,NI于5～14 d PCNA阳性细胞率逐渐增多,14 d达高峰,28 d后开始逐渐减少,但NI阳性率多于中膜.③S组中膜SMα-actin表达为阳性,内皮为阴性;中膜阳性面积于损伤后1 d开始减少,3 d最为明显,5 d后开始逐渐增加,NI阳性表达弱于中膜.④S组中膜MKP-1呈弱阳性或阳性表达,损伤后1d即开始下降,5～7 d达最低,14 d稍有回升,至35 d仍未回到假损伤组水平;NI阳性表达弱于中膜.MKP-1表达变化与PCNA表达变化呈负相关.结论:VSMC增殖能力与其表型转化密切相关,MKP-1参与了损伤后VSMC表型转化的调节.The model of vascular restenosis established by balloon injury of rabbit carotid arteries was used. HE staining, immunohistochemistry and reverse transcriptase-polymerase chain reaction （RT-PCR） were used to detect the change of proliferation cell nuclear antigen （ PCNA ）, smooth muscle α-actin （ SMα-actin）, MKP-1 mRNA and protein expression, and morphology of sham-injured group and injury groups at different time. RESULTS ： The proliferation of VSMC was observed on the side of the medium lumen at I d and on the surface of vascular lumen at 3 d after injury. The neointima was formed and gradually getting thickening at 5 -7 d, and thickening was more obvious and rapid at 14 -35 d. The expression of PCNA was negative in the medium and endothelium in sham-injured group. Positive cell rate of PCNA was gradually increased at 1 - 14 d in the medium and at 5 - 14 d in the neointima, reaching maximum at 14 d and declining gradually at 28 d. Positive cell rate of PCNA in the neointima was higher than that in the medium. Expression of SMα-actin was positive in the medium, negative in the endothelium in sham-injured group.Positive cell area of SMα-actin began to decrease at 1 d in the medium, getting to the minimum at 3 d and started to increase at 5 d. Expression of SMα-actin in the neointima was lower than in the medium. Expression of MKP-1 was feeble positive or positive in sham-injured group. Expression of MKP-1 initially decreased at 1 d, reaching lowest value at 5 -7 d, increased gradually from 14 d. MKP-1 was negatively correlated with PCNA in the vascular wall after injury. CONCLUSION： There is a close relationship between phenotypic modulation and proliferation ability of VSMC. MKP-1 participates in regulation of phenotypic modulation of VSMC after intimal injury.

关 键 词：内膜损伤 血管平滑肌细胞 表型转化 丝裂原激活蛋白激酶磷酸酶-1 

分 类 号：R543.5[医药卫生—心血管疾病]