Development and clinical application of novel anti-atherogenic drug.

建立了抑制单核细胞粘附血管内皮细胞的实验系统。内皮细胞来源于人脐静脉。将内皮细胞与1,3-二硫醇-2-基戊二酸二异丙酯或抗vcam -1抗体共孵育，观察其抑制作用。遗憾的是，二异丙基-1,3-二硫醇-2-基戊二酸酯的抑制作用有限，不能重复实验。对于抗vcam -1抗体，实验正在进行中。我们使用兔子系统，因为我们有一个很好的动物模型来研究家族性高胆固醇血症，whhl -兔子，它一出生就有严重的胆固醇血症和动脉粥样硬化。因此，我们选择VCAM-1作为兔单核细胞的粘附分子。研究发现，VCAM-1分子在1月龄时开始在第一肋间动脉孔口表面表达。此外，在同一区域观察到单核细胞的积累。2月龄时，在第一肋间动脉处的动脉壁周围可见VCAM-1的表达。3个月大时，在同一部位可见T淋巴细胞。这些现象都是首次观察到的，所以我们正在准备稿件发表。最近，VCAM-1基因敲除小鼠被其他科学家制成。根据敲除小鼠的研究，几种粘附分子参与单核细胞在内皮细胞上的附着。除了VCAM-1分子外，我们正在寻找体内内皮细胞上单核细胞粘附的粘附分子。

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.