Background Lipoprotein-associated phospholipase A2 （Lp-PLA2） is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein （HDL） plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive. Methods In this study, reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting, and a platelet-activating factor （PAF） acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ （PPARy） ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined. Results Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment （1-10 ng/ml） upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARy phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL. Conclusion These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.
HAN Guan-pingREN Jing-yiQIN LiSONG Jun-xianWANG LanCHEN Hong
目的系统评价他汀类药物联用非诺贝特的安全性。方法检索1981至2013年Medline、Cochrane Library、Web of Knowledge和中国知网数据库中的随机对照临床试验，采用RevMan5．0软件对所纳入的数据进行荟萃分析。共检索2184篇相关文献，有26篇文献入选，26项随机对照临床研究共纳入9494例患者。结果他汀类药物联合非诺贝特组转氨酶升高的风险明显高于单药他汀组（OR1．67，95％CI1．22—2．30，P〈0．05）。肌酸激酶升高（OR0．86，95％CI0．62—1．20，P〉0．05）、肌肉不良反应（OR 0．98，95％CI0．88—1．09，P〉0．05）、肝功异常和肌肉不良反应导致退出的发生率两组问差异无统计学意义。常规剂量他汀类药物联合非诺贝特的安全性与总剂量他汀类药物联合非诺贝特相似。结论他汀类药物联用非诺贝特具有良好的安全性和耐受性，不增加肌肉不良反应的风险。联合用药时要定期检测转氨酶，防止发生肝功能异常。
