Development and clinical application of novel anti-atherogenic drug.

建立了单核细胞与血管内皮细胞粘附抑制作用的实验体系。内皮细胞来源于人脐静脉。将内皮细胞与或不与1，3-二巯基-2-亚基丙二酸二异丙酯或抗VCAM-1抗体共孵育，并检测这些试剂的抑制作用。不幸的是，二异丙基-1，3-二硫醇-2-亚基丙二酸酯的抑制作用有限，而不是重复实验。在抗VCAM-1抗体的情况下，正在进行实验。我们采用兔系统，因为我们有一个很好的动物模型，家族性高胆固醇血症，WHHL兔，这是严重的胆固醇血症和动脉粥样硬化，因为它出生以来。结果表明，VCAM-1分子在1月龄兔第一肋间动脉口表面开始表达，并有单核细胞聚集。2月龄时，VCAM-1表达于第一肋间动脉处的动脉壁周围。3月龄时，在同一部位可见T淋巴细胞。这些现象是首次观察到的，所以我们正在准备出版的手稿。最近，其他科学家制造了VCAM-1敲除小鼠。基因敲除小鼠的研究表明，体内有多种粘附分子参与单核细胞与内皮细胞的粘附。除VCAM-1分子外，我们还在体内寻找与单核细胞在内皮细胞上粘附有关的粘附分子。

We established assay system by which the inhibiting effect of monocyte adhesion to vascular endothelial cell is examined. The source of endothelial cells are from human umbilical vein. The endothelial cells were coincubating with or without Diisoprophyl-1,3-dithiol-2-ylidenemalonate or anti-VCAM-1 antibody and the inhibiting effect of these agents were examined. Unfortunately, the inhibiting effect of Diisoprophyl-1,3-dithiol-2-ylidenemalonate was limited, instead of repeat experiments. In case of anti-VCAM-1 antibody, experiments is undergoing. We use rabbit system, because we have an excellent animal model for familial hypercholesterolemia, WHHL-rabbit, which has severe cholesterolemia and atherosclerosis, since it is born. Therefore we chose VCAM-1 as an adhesion molecule for rabbit monocytes.It has been found that VCAM-1 molecules started to express on the surface of orifice for first intercostal artery at one month of age.In addition, the accumulation of monocytes were observed at the same area. At two month of age, the expression of VCAM-1 were found around the arterial wall at the place of first intercostal artery. At three month of age, T lymphocytes were seen at the same area. These phenomenon are first observation, so we are preparing the manuscript for publication. Recently VCAM-1 knockout mouse was made by other scientists. According to the study of knockout mouse, several adhesion molecules are involving the monocyte attachment onto endothelial cells in vivo. We are now searching adhesion molecules which are involving the monocyte attachment on the endothelial cells in vivo, besides VCAM-1 molecule.