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脂蛋白a促进终末期肾病患者动脉粥样硬化进展
作者:贡铁凯  弓玉祥  胡泽波  张洋  王桂花  刘亮  鲁荐  陈佩佩  芦琛琛  倪海峰  刘必成  马坤岭 
单位:东南大学附属中大医院/肾内科 肾脏病研究所, 江苏 南京 210009
关键词:脂蛋白a 动脉粥样硬化 低密度脂蛋白受体 趋化因子CXC配体16 终末期肾病 
分类号:R692;R543.5
出版年·卷·期(页码):2017·36·第十一期(1537-1543)
摘要:

目的:研究脂蛋白a(lipoprotein a,Lpa)在终末期肾病(end-stage renal disease,ESRD)动脉粥样硬化中的作用,并进一步探讨CXC趋化因子配体16(CXC chemokine ligand 16,CXCL16)和低密度脂蛋白受体(low density lipoprotein receptor,LDLr)是否介导了Lpa的胞内摄入。方法:根据血浆Lpa质量浓度将46例ESRD患者分为对照组[ρ(Lpa)<300 mg·L-1n=23]和高Lpa组[ρ(Lpa)≥300 mg·L-1n=23]。检测两组患者的生化指标和脂质谱。取ESRD患者动静脉内瘘手术时桡动脉边缘切除的组织,HE染色观察其泡沫细胞形成、Filipin染色观察其胆固醇沉积;免疫组化和免疫荧光染色观察其Lpa的沉积;免疫组化观察LDLr和CXCL16的表达;免疫荧光共染分别观察Lpa和LDLr、Lpa和CXCL16的共表达。结果:与对照组比较,高Lpa组ESRD患者的桡动脉中泡沫细胞增多、胆固醇沉积增加、Lpa沉积增加、CXCL16和LDLr表达增加(均P<0.05);相关性分析显示,血浆Lpa质量浓度与Lpa沉积程度(r=0.72,P<0.01)、LDLr表达(r=0.54,P<0.01)、CXCL16表达(r=0.6,P<0.01)均呈正相关。进一步免疫荧光共染发现,高Lpa组的桡动脉组织中Lpa与LDLr、CXCL16共表达均增加(均P<0.05)。结论:Lpa在ESRD患者桡动脉中沉积,促进泡沫细胞形成,进而导致动脉粥样硬化的发生,LDLr和CXCL16可能是介导Lpa进入桡动脉组织细胞内的主要脂蛋白受体。

Objective:To explore the role of lipoprotein a(Lpa) in the progression of atherosclerosis(AS) in end-stage renal disease(ESRD) and further investigate its potential mechanism mediated by CXC chemokine ligand 16(CXCL16) and low density lipoprotein receptor(LDLr). Methods:46 ESRD patients were divided into control group[ρ(Lpa)<300 mg·L-1,n=23] and high concentration of Lpa group[ρ(Lpa) ≥ 300 mg·L-1,n=23] according to plasma Lpa level. Biochemical indexes and lipid profile of patients were measured. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments for preliminary evaluation of AS. Hematoxylin-eosin(HE) and Filipin staining were used to observe foam cell formation. Protein expressions of Lpa, CXCL16, and LDLr were detected by immunohistochemistry staining and immunofluorescence staining. Results:More foam cells and cholesterol accumulation were seen in the arteries of patients in high concentration of Lpa group when compared with the control. Meanwhile, the expressions of Lpa, CXCL16, and LDLr were significantly increased in the arteries of patients in high concentration of Lpa group. Correlation analysis showed that the protein expressions of Lpa(r=0.72, P<0.01), LDLr(r=0.54,P<0.01) and CXCL16(r=0.6,P<0.01) in arteries of ESRD patients were positively correlated with plasma Lpa level. Further analysis showed that the co-expression of Lpa and LDLr was increased in high concentration of Lpa group, as well as the co-expression of Lpa and CXCL16. Conclusion:High plasma Lpa level contributes to the progression of AS in ESRD by inducing the Lpa accumulation. LDLr and CXCL16 could be the main lipoproteins by which Lpa enters the cells of arteries.

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