冠心病不稳定斑块凋亡相关基因表达紊乱的机制研究

目的探讨冠心病不稳定斑块中凋亡相关基因的表达情况及调控机制。方法86例冠心病患者，其中不稳定组42例，稳定组44例。取两组冠脉斑块标本，Northern Blot和Western Blot检测Bax、caspase-3和凋亡相关蛋白激酶（DAPK）的表达水平，并与正常对照组进行比较。结果对照组和稳定组的caspase-3表达水平基本类似（P〉0．05），不稳定组约为其他组的2倍（P〈0．01）；不稳定组的Bax和DAPK表达达到对照组的3倍和6倍（P〈0．01）。对照组冠脉平滑肌细胞（VSMC）置于LDL中培养，细胞凋亡率显著上升（P〈0．01）；caspase-3的表达上升幅度为正常状态的1．5倍（P〈0．05），Bax和DAPK的上升均达到正常细胞的3倍（P〈0．01）。结论冠状动脉粥样硬化（CAS）组织中，高浓度LDL诱发凋亡相关基因表达紊乱是导致细胞凋亡失衡的重要原因，其中Bax和DAPK可能是这一调控途径中的关键分子。

Study on mechanism of disorder expression of apoptosis-related genes in unstable plaques of coronary heart disease

Objective To determine the expression of apoptosis-related genes in unstable plaques of CHD and its relation to low density lipoprotein(LDL).Methods Among 86 patients with CHD,there were 42 cases with ACS(unstable group), and the other 44 cases were taken as stable group.The expression of Bax,caspase-3 and death-associated protein kinase(DAPK) in the specimens and normal controls was detected.After incubated with LDL,cell apoptosis and expression profiling of apoptosis-related genes in control groups was assessed.Results Expression of caspase-3 was similar in the stable and control groups(P>0.05),and that in unstable group was 2-fold.The levels of Bax and DAPK in unstable group increased to 3-fold and 6-fold as compared with those of controls(P<0.01).Treated with LDL,the apoptosis ratio in control group VSMC upregulated significantly with time increasing(P<0.01),the enhanced levels of Bax and DAPK were apparent (P<0.01).Conclusions High concentration of LDL leads to disorderly cell apoptosis and upregulation of apoptosis-related genes in unstable plaques.Bax and DAPK may play a key role in this regulatory pathway.