摘要
目的:研究可溶性凝血酶调节蛋白(Soluble thrombomodulin,sTM)结合的血浆低密度脂蛋白对细胞胆固醇代谢的影响,探索sTM参与或影响动脉粥样硬化发病过程的初步机制。方法:以THP-1巨噬细胞为模型,通过油红O染色、高效液相色谱检测胆固醇含量等方法,以体外重组人可溶性凝血酶调节蛋白结合的低密度脂蛋白(sTM-LDL)作用于巨噬细胞,观察sTM-LDL对细胞胆固醇代谢的影响。结果:研究发现:正常人LDL对细胞内胆固醇代谢影响较小;而sTM-LDL处理细胞72小时后,细胞内大量脂滴形成,细胞内胆固醇含量明显增多,符合典型泡沫细胞的特征;运用NH-1单抗中和／干扰sTM的作用,不能阻断sTM-LDL诱导的THP-1细胞内胆固醇聚集。结论:sTM对LDL的修饰可能改变了LDL的理化特性和代谢途径,可导致细胞内胆固醇聚集和泡沫细胞的形成,且这种作用与sTM本身对细胞的影响可能无明显关系。
Objective： To explore the influence of plasma sTM-LDL （=Soluble thrombomodulin, low density lipoprotein） on celluar cholesterol metabolism. Methods： Cellular cholesterol content of THP-1 macrophages, which were treated by the binding of recombinant soluble Thrombomodulin to LDL（sTM-LDL）, were determined by using Oil Red O dyeing and high performance liquid chromatogram（HPLC）. Results： The results showed that NLDL （80mg/ml） treatment for THP-1 macrophages 72 hours had no significantly change in cellular cholesterol contents. However, after THP-1 was treated with the same amount of sTM-LDL, Oil Red O dyeing and HPLC experiment showed that THP-l,after being treated with sTM-LDL for 72 hours, formed a typical foam cell shape with a large number of lipid droplets. Meanwhile, the monoclonal antibody against TM （NH-1） did not inhibit the effects of sTM□LDL. Conclusion： These data suggest that the binding of sTM to LDL may be newfashioned modification of LDL. The sTM modified LDL, which can interfere cellular cholesterol metabolism, and induce foam cell formation derived from macrophages, which may play an important role in atherosderosis.
出处
《现代生物医学进展》
CAS
2007年第3期356-357,366,共3页
Progress in Modern Biomedicine
基金
湖南省自然科学基金项目(04JJ3060
04Jjy2145)
