癌基因及抗癌基因在实验性动脉粥样硬化斑块中的转录表达

Transcriptional Expression of Oncogenes and Rb Antioncogene in Experimental Atherosclerotic Lesions *

本研究以高胆固醇膳食饲养家兔建立了主动脉粥样硬化模型，选用ｖ－ｓｉｓ等６种癌基因和Ｒｂ抗癌基因片段为探针，分别与硬化斑块动脉壁及正常动脉壁总ＲＮＡ进行斑点杂交分析。结果表明，ｖ－ｓｉｓ、ｃ－ｆｏｓ和ｃ－ｍｙｃ癌基因表达与正常对照比较增加３倍以上（Ｐ＜０．０１），ｃ－ｊｕｎ和Ｈ－ｒａｓ表达增加２倍（Ｐ＜０．０１），ｖ－ｅｒｂ－Ｂ表达无改变，Ｒｂ抗癌基因表达显著减少（Ｐ＜０．０５）。这些结果提示，动脉粥样硬化斑块的形成及动脉平滑肌细胞的增殖可能与ｖ－ｓｉｓ，ｃ－ｆｏｓ，ｃ－ｍｙｃ，ｃ－ｊｕｎ，Ｈ－ｒａｓ等癌基因的表达增强及Ｒｂ抗癌基因表达减弱有关。

Atherosclerosis (AS)is characterized by the proliferation of the smooth muscle cells (SMC) in the arterial wall. Its pathogenesis might be associated with overexpression of oncogenes in SMC. Gorden and Barrett et al found that sis mRNA level elevated in human atherosclerotic plaques 5 12 fold above level present in normal artery. But the transcriptional expression of c fos, c myc, c jun, H ras, v erb B oncogenes and Rb antioncogene in atherosclerotic lesion has not yet been reported. A study on these oncogenes and Rb gene expression in artherosclerotic lesions in rabbits fed on high cholesterol diet were assayed by the dot blot hybridization using α 32 P labelled oncogenes and Rb gene fragments as the probes. After fed with the high cholesterol diet for six months,the plasma cholesterol levels in AS rabbits were significantly increased (1300±240mg/dl vs 67.1±11.5 mg/dl). The atherosclerotic plaques covered 91%± 11% of the intimal aortic surface of aorta thoracalis. The results showed that the atherosclerotic plaques contained 3 4 fold more v sis, c fos and c myc mRNA ( P <0.01),2 fold more c jun and H ras mRNA( P < 0.01), and less Rb mRNA( P <0.05) than those in the normal aortic arteries. But the expression of v erb B gene in atherosclerotic plaques remained unchanged. These results indicate that the abnormal expression of v sis, c myc, c fos, c jun, and H ras oncogenes and Rb antioncogene may play an important role in arterial SMC proliferation and pathogenesis of atherosclerosis.