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目的 探讨高同型半胱氨酸 (HCY)血症引起心血管病和出生性缺陷的作用机制。方法 采用诱导筛选方法克隆高同型半胱氨酸诱导基因 HCY- 2 ,以 Northern印迹分析检测 HCY- 2基因在大鼠不同组织中的表达 ,以免疫组化方法验证 HCY- 2蛋白在大鼠不同组织中的表达。结果 以诱导筛选方法从大鼠血管平滑肌细胞内克隆到一个新的全长 c DNA,即高同型半胱氨酸诱导基因 HCY- 2 ,它编码 142个氨基酸。Northern印迹分析和免疫组化检测表明 ,HCY- 2基因可在大鼠心、肾、脑、肝、肺等组织中广泛表达。在体外 ,将重组 HCY- 2基因转移至内皮细胞中 ,能够引起细胞凋亡和 DNA损伤 ;在体内 ,将 HCY- 2基因转移至鸡胚内 ,则诱发鸡胚细胞凋亡 ,并引起畸形。结论 HCY- 2基因可能是一种新的凋亡基因 ,高同型半胱氨酸血症可能通过 HCY- 2基因诱发心血管病和出生性畸形。
Objective To investigate the mechanism of cardiovascular diseases and birth defects caused by hyperhomocysteine (HCY). Methods High homocysteine-induced gene HCY-2 was cloned by induction screening method. The expression of HCY-2 gene in different tissues of rats was detected by Northern blot analysis. The expression of HCY-2 protein was detected by immunohistochemistry in rats Expression in tissue. Results A new full-length c DNA was cloned from rat vascular smooth muscle cells by induction screening. That is, the homocysteine-induced gene HCY-2 encoded 142 amino acids. Northern blot analysis and immunohistochemistry showed that HCY-2 gene was widely expressed in the heart, kidney, brain, liver, lung and other tissues. In vitro, the transfer of recombinant HCY-2 gene into endothelial cells can cause apoptosis and DNA damage. In vivo, the transfer of HCY-2 gene into chicken embryos induces apoptosis in chick embryo cells and leads to deformity. Conclusion The HCY-2 gene may be a new apoptotic gene. Hyperhomocysteinemia may induce cardiovascular disease and birth deformity through HCY-2 gene.