目的研究氧化型低密度脂蛋白通过IL-22对人脐静脉内皮细胞(CRL-1730)增殖的影响及机制,初步探讨IL-22与冠状动脉粥样硬化(AS)发病机制的关系。方法采用RT-PCR检测8例无明显冠状动脉狭窄的健康个体和30例AS患者外周血单个核细胞(PBMC)IL-22mRNA的表达,ELISA法检测22例无明显冠状动脉狭窄的健康个体和79例AS患者血浆IL-22的浓度,分析IL-22的表达与AS患者冠状动脉最大狭窄程度及受累支数的关系。使用不同浓度氧化型低密度脂蛋白(OX—LDL)刺激CRL-1730细胞,24h后流式细胞术检测IL-22R1阳性细胞百分比。100μg/mlOX-LDL和20ng/mlIL-22共刺激CRL-1730细胞后,MTS法检测细胞的增殖能力,RT-PCR和ELISA检测碱性成纤维细胞生长因子(bFGF)的表达。结果随着患者冠状动脉狭窄程度和受累支数的增加,AS患者外周血PBMC中IL-22mRNA和血浆中IL-22水平逐渐降低。OX-LDL呈剂量依赖性地上调CRL-1730细胞中IL-22R1的表达。OX-LDL刺激可以引起CRL-1730细胞增殖能力受损、表达bFGF的能力降低,IL-22可以部分逆转OX—LDL的此种效应。结论IL-22可能具有抗AS的生物学效应,这种生物学效应可能与其拮抗OX-LDL对CRL-1730细胞增殖能力和表达bFGF的抑制作用有关。
Objective To investigate the association between IL-22 and the pathogenesis of coro- nary artery atherosclerosis (AS). Methods The relative expression of IL-22 mRNA in PBMC from 30 AS patients and 8 patients without any signs of coronary artery stenosis was detected by RT-PCR. Serum IL-22 levels of 22 patients without any signs of coronary artery stenosis and 79 AS patients were detected by ELISA. CRL-1730 cells( human umbilical vein endothelial cells) were stimulated with oxidized low density lipoprotein (ox-LDL) at different dosage for 24 h, and the expression of IL-22R1 was detected by flowcytom- etry. The proliferation ability of CRL-1730 cells treated with IL-22(20 ng/ml) and/or ox-LDL( 100 I~g/ml) was measured by MTS assay, and the expression of basic fibroblast growth factor(bFGF) was detected by RT- PCR and ELISA. Results Decreased IL-22 expression in PBMC and serum was observed as worsen of AS. The expression of IL-22R1 in ox-LDL treated CRL-1730 cells was increased in dose dependent manner. Ox- LDL decreased proliferation ability, as well as bFGF expression and releasing, of CRL-1730 ceils. This effect of ox-LDL was partially rescued by IL-22. Conclusion IL-22 may have anti-atherosclerosis effect. This effect may be mediated by regulating bFGF expression and endothelial cells proliferation ability in the pres- ence of IL-22.