Development and clinical application of novel anti-atherogenic drug.

我们建立了检测单核细胞与血管内皮细胞黏附抑制作用的检测体系。血管内皮细胞的来源是人脐静脉。将血管内皮细胞与1，3-二硫醇-2-亚甲基丙二酸二异丙酯或抗血管细胞黏附分子-1抗体共同孵育，检测其对内皮细胞生长的抑制作用。遗憾的是，1，3-二硫醇-2-亚甲基丙二酸二异丙苯酯的抑制作用是有限的，没有重复实验。在抗VCAM-1抗体的情况下，正在进行实验。我们使用兔系统，因为我们有一个很好的家族性高胆固醇血症的动物模型，WHHL-兔，它自出生以来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作为兔单核细胞的黏附分子，发现VCAM-1分子在1个月龄时就开始在第一肋间动脉的开口表面表达，并在同一区域观察到单核细胞的聚集。2月龄时，VCAM-1在第一肋间动脉处的动脉壁周围有表达。3月龄时，同一区域可见T淋巴细胞。这些现象是第一次观察到的，所以我们正在准备出版手稿。最近，其他科学家研制出了VCAM-1基因敲除小鼠。根据对基因敲除小鼠的研究，体内有几种黏附分子参与了单核细胞与内皮细胞的黏附。目前，除了VCAM-1分子外，我们还在寻找与单核细胞在体内内皮细胞的黏附有关的黏附分子。

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.