冠心病危险因素促使人外周血单核细胞高表达尿激酶型纤溶酶原激活物受体的研究

Risk factors for coronary artery disease stimulate urokinase receptor expression on monocytes

目的分析冠心病危险因素对人外周血单核细胞上尿激酶型纤溶酶原激活物受体(uPAR)表达的影响。方法入选2005年8月至2006年3月门诊或住院的单纯高血压患者16例,单纯脂质异常患者24例,高血压合并肥胖患者18例,脂质异常合并肥胖患者18例,脂质异常高血压合并肥胖患者30例以及健康志愿者17例。每例抽取静脉血,用异硫氰酸荧光素标记的小鼠抗人CD14单克隆抗体(CD14-FITC)和藻红蛋白标记的小鼠抗人 uPAR(CD87)单克隆抗体(CD87-PE)染色;以小鼠抗人 IgG2a,k 替代 CD87-PE 作同型对照。流式细胞仪检测外周血 uPAR 阳性的单核细胞比例及单核细胞上 uPAR 的平均荧光强度(MFI)指数。结果单纯高血压患者外周血中 uPAR 阳性的单核细胞比例为(4.9±12.5)%,较之对照组的(7.7±10.3)%,差异无统计学意义;单纯脂质异常患者该比例升至(23.7±22.5)%,较前两组分别增加3.9倍和2.1倍,P<0.05。当合并肥胖时,表达uPAR 的单核细胞比例进一步升高,高血压肥胖组、脂质异常肥胖组、脂质异常高血压肥胖组分别为(32.9±30.8)%,(37.4±31.4)%和(23.8±20.5)%,与高血压组和对照组比较,均有统计学意义(均 P<0.01);校正各组年龄、体重和高敏 C 反应蛋白后,上述差异仍然存在。脂质异常组和高血压肥胖组单核细胞上 uPAR 的 MFI 指数分别为1.91±1.97和2.33±2.52,均高于对照组的0.78±0.86,P<0.05。脂质异常组 uPAR 的表达与空腹血糖水平存在直线相关关系(r=0.72,P=0.04)。结论冠心病危险因素可以显著刺激外周血单核细胞表面 uPAR 的表达,血脂异常或肥胖是引起uPAR 高表达的重要因素。

Objective To evaluate the effect of risk factors for coronary artery disease （CAD） on urokinase receptor（uPAR） expression on monocytes. Methods A total of 106 patients were enrolled and divided into five risk-factor groups： sixteen with hypertension, twenty-four with dyslipidemia, eighteen with hypertension ＋ obesity, eighteen with dyslipidemia ＋ obesity and thirty with hypertension ＋ dyslipidemia ＋ obesity. Seventeen healthy volunteers were recruited as control group. Monocyte expression of uPAR and mean fluorescence intensity index （MFI Index） of uPAR were measured by flow cytometer （FACSCalibur）. Results No difference in moncocyte u-PAR expression was detected between hypertension and control group [ （4. 9±12. 5）% vs. （7.7 ±10. 3）%, P=0.74]. However, the uPAR expression was raised to （23.7 ± 22. 5 ） % in hyperlipidemia group, a 3. 9- and a 2. 1-fold increase compared with those in hypertension （ P 〈 0. 01 ） and control group （ P 〈 0. 05 ）, respectively. When combined with obesity, u-PAR expression was elevated further to （32.9 ± 30. 8 ） % in hypertension ＋ obesity group, （ 37.4 ± 31.4 ） % in dyslipidemia ＋ obesity group and （23.8 ± 20. 5） % in hypertemion ＋ dyslipidemia ＋ obesity group, all having statistical significance compared with control group or hypertension group （ P 〈 0. 01 ）. The results were the same when corrected by age, BMI and hs-CRP, uPAR MFI Index was increased from 0. 78 ± 0. 86 in control group to 1.91 ± 1.97 and 3.33 ± 2. 52 in dyslipidemia group and hypertemion ＋ obesity group, respectively, P 〈 0. 05. Linear regression analysis revealed a significant correlation between uPAR expression and FBG concentration in dyslipidemia group, r = 0. 72, P = 0. 04. Conclusions uPAR expression was elevated on monocytes in patients with risk factors for CAD. Dyslipidemia and obesity may contribute to the increase of uPAR expression.