中国成人动脉粥样硬化病变中p53抑癌基因的结构突变及与病变程度的关系

应用ＰＣＲ－ＳＳＣＰ方法，系统地研究了中国成人动脉粥样硬化（ＡＳ）病变组织中ｐ５３抑癌基因结构的突变及与病变程度之间的关系。结果：受检的８９例ＡＳ组织中的９例发现有ＰＣＲ－ＳＳＣＰ的异常，其中６例经测序证实ｐ５３基因突变的具体内容。在此基础上，应用高特异性的ｐ５３蛋白单克隆抗体，证实在有ｐ５３基因突变的ＡＳ组织中也同时有ｐ５３突变蛋白的异常表达；对动脉管腔狭窄面积、斑块的相对厚度及二者与ｐ５３基因突变之间关系的弹力纤维特殊染色及计算机定量图像分析结果显示：ｐ５３基因突变组的管腔狭窄面积明显严重于无突变组（Ｐ＜０．０２５），ＡＳ组织的相对厚度也明显大于无突变组（Ｐ＜０．０５～０．０１）。结论：在人类的ＡＳ病变中存在有ｐ５３抑癌基因的突变；该基因的突变与ＡＳ病变的严重程度密切相关，并可能是ＡＳ形成的一个新的、重要的机制。

The mutations of p53 anti oncogene and the relation to the severity of atherosclerotic lesions in Chinese adults

Controlling by Chinese healthy adults normal artery cells and healthy adults normal blood lymphocytes (DNA), the mutations of p53 anti oncogene in atherosclerotic (AS) plaques of 89 Chinese adults were studied systematically. Mutations of p53 gene were found in 9 cases (9/89) by radiative PCR SSCP; the abnormal stains of p53 protein could also be detected by high specifity monoclone antibody of p53 protein p53 DO 1. Using the improved Victoria blue/Nuclear fast red, a special stain for internal elastic membrane, the borderline between AS plaques with normal vascular walls could be distinguished very clearly. The AS plaques could be distinguished by computer, and the severity and the extent of the AS lesions could be quantitatively analyzed. It is found that the vascular remaining area ratio (R.1) in group of p53 gene mutations was remarkably small than that in group of non mutations (0.6487 vs 0.7371, P <0.025), and the relative vascular palque thickness ratio (R.2) in group of mutation were also remarkably larger than that in group of non mutation (0.5814 vs 0.4439, 0.4618 vs 0.3061, P <0 05 0 01).It is suggested that the mutations of p53 gene have some critical relations to the extent of human AS lesions, and also this is probably a new and important pathogenesis for AS formation.