氧化型脂蛋白（a）对大鼠GMCs增生及ICAM-1表达的影响

目的探讨氧化型脂蛋白（a）Ox-Lp（a）]对大鼠肾小球系膜细胞（GMCs）增生及细胞闻粘附因子-1（ICAM-1）表达的影响。方法分离Lp（a）并氧化修饰，培养GMCs，分别加入终浓度2、5、5、10、20nmol／L的Ox-Lp（a）作用12h，终浓度5nmol／L的OX-Lp（a）作用12h、24h、48h、60h。采用MTT法测定GMCs增生率，免疫组化法检测GMCs的增生细胞核抗原（PCNA）阳性表达率，酶联免疫法检测培养液上清的ICAM-1浓度。并与加入终浓度5nmoL／L的天然Lp（a）n-Lp（a）]作用12h的Lp（a）组及不加任何刺激因素的空白对照组比较。结果与对照组比较，Lp（a）组GMCs的MTr增生率、PCNA阳性率、培养上清ICAM-1含量明显增高，差异有统计学意义（P〈0．01）。与Lp（a）比较，Ox-LD（a）刺激后的GMCs MTT增生率、PCNA阳性率、培养上清ICAM-1含量明显增高，且Ox—Lp（a）2．5nmoL／L作用高于终浓度5nmoL／L的Lp（a）组（P〈0．01）。随着Ox—Lp（a）浓度的增加，GMCs的MTT增生率、PCNA阳性率、培养上清ICAM-1含量呈明显变化，Ox—LF（a）5nmol／L时达高峰，在Ox-Lp（a）10nmoL／L组出现下降，20nmoL／L明显下降，差异有统计学意义（P〈0．01）。随着处理时间的延长，GMCs的MTT增生率、PCNA阳性率、培养上清ICAM-1含量呈上升趋势，48h达到高峰，60h出现下降（P〈0.01）。GMCs上清的ICAM-1浓度与MTT和PCNA阳性表达率呈正相关（P〈0．01）。结论Lp（a）、Ox—Lp（a）能明显影响GMCs的增生，Ox-Lp（a）生物学作用强于Lp（a）。Ox—Lp（a）对GMCs的作用呈剂量依赖性和时间依赖性，小剂量时刺激GMCs的增生，大剂量则表现为细胞毒作用。Ox—Lp（a）明显影响大鼠GMCs的ICAM-1表达，GMCs上清的ICAM-1浓度与MTT和PCNA阳性表达率呈正相关。提示Ox—Lp（a）对肾小球系膜细胞的作用可能与ICAM-1有关。

Regulation of intercellular adhesion molecule-1 expression on murine glomerular mesangial cells by Oxidized lipoprotein(a)

Objective To investigate the effects of oxidized lipoprotein （a） Ox - Lp （a）] on proliferation of glomerular mesangial cells （GMCs） and the experssion of intercellular adhesion molecule - 1 （ICAM - 1 ） in rat model induced by lipopolysaccharide, and explore the possible mechanism of Ox - Lp（a） on the proliferation of rat GMCs. Methods The effect of Ox- Lp（a） with different doses of 2.5, 5, 10, and 20nmol/L on the proliferation of GMCs was observed. The rats of were divided into three groups： control group, Lp（a） group, Ox - Lp（a） group. After culture （at the end of 12h, 24h, 48h and 60h）, the cultured GMCs and suspension were collected for observation of the proliferative rate of GMCs （MTT）, the positive rate of proliferationg cell nuclear antigen （PCNA）（immuno - histo - chemisty）, and ICAM- 1 activity was determined with ELISA. Results At the end of experiment, compared with control and Lp（a） group , MTT, positive rate of PCNA and ICAM - 1 activity of GMCs were more significantly higher in Ox- Lp（a） group; as for dosage - response, MTT, the positive rate of PCNA and ICAM- 1 activity of GMCs were increased as Ox - Lp（a） doses increased, a maximal effect was seen for Ox - Lp（a） 5nmol/L group. Alon with the continuous increaseOx- Lp（a） 10nmol/L], MTT, the positive rate of PCNA and ICAM- 1 activity of GMCs were decreased in Ox - Lp（a） group; As for time - response, MTT, the positive rate of PCNA and ICAM - 1 activity were increased as Ox -Lp（a） dosage increased, a maximal effect was seen for Ox- Lp （a） cultured GMCs 48h. ICAM - 1 activity showed positive correlation with MTT and the positive rate of PCNA. Conclusion Ox - Lp （a） can significantly affect the rate of GMCs proliferation, this effect is dosage - dependent and time - dependent. Small dosage can stimulate proliferation of GMCs, bigger dosage inhibit the proliferation of GMCs. Ox - Lp（a） can significantly affect ICAM - 1 activity, too. ICAM - 1 activity is positivel