基因芯片在同型半胱氨酸诱导动脉粥样硬化基因表达谱变化中的应用

应用基因芯片技术研究同型半胱氨酸诱导动脉粥样硬化的基因表达谱变化。选取3例无冠心病传统危险因素的住院患者，其中1例为血同型半胱氨酸正常的冠状动脉造影正常者，1例为血同型半胱氨酸正常的冠心病患者，1例为高同型半胱氨酸血症的冠心病患者。分离外周血淋巴细胞并抽提总RNA，逆转录制备杂交探针，应用含有1152条基因的人类表达谱芯片进行差异表达谱分析。结果发现，高同型半胱氨酸血症的冠心病患者与血同型半胱氨酸正常的冠状动脉造影正常者比较差异表达的基因177条(组一)，高同型半胱氨酸血症的冠心病患者与血同型半胱氨酸正常的冠心病患者比较差异表达的基因有151条(组三)。组一与组三基因芯片平行比较，二者共同的差异表达基因48条，其中上调基因23条，下调基因25条。结果提示，在差异表达的基因中，有些是凋亡、信号转导、免疫、蛋白质合成及原癌基因等的相关基因，这些基因可能与同型半胱氨酸致动脉粥样硬化发生有关。应用基因芯片技术研究同型半胱氨酸诱导动脉粥样硬化差异表达谱，可能为动脉粥样硬化发病机制研究提供新的思路。

Analysis of Gene Expression Patterns in Atherosclerosis Induced by Homocysteine Using cDNA Microarray

Aim To investigate gene expression patterns of atherosclerosis (As) induced by homocysteine (Hcy). Methods Total RNA were isolated from peripheral blood lymphocytes of 3 inpatients who had no traditional risk factors of coronary heart disease (CHD). They were one with normal coronary angiography and plasma Hcy level, one CHD patient with normal plasma Hcy level, and one CHD patient with high plasma homocysteine level. The RNAs were reversely transcribed to the cDNAs to prepare the hybridization probes. The probes were hybridized to the gene chip with 1152 genes to study gene expression patterns. Results There were 177 differentially expressed genes between the CHD patient with high plasma homocysteine level and the patient with normal coronary angiography and plasma Hcy level (group 1). There were 151 differentially expressed genes between the CHD patient with high plasma homocysteine level and the CHD patient with normal plasma Hcy level (group 3). A parallel comparison between group 1 and group 3 gene chips showed that there were 48 differentially expressed genes in common, of which there were 25 down-regulated and 23 up-regulated genes. Conclusion Among the differentially expressed genes, some are involved in the functions of apoptosis, signal transduction, immunology, translation of protein and proto-oncogene, etc. They had potential values in genesis of As induced by Hcy. The study based on gene chip in researching the differentially expressed genes of As induced by Hcy will provide new clues for finding out the pathogenesis of As.