Cross talk of oxidative and chronic mental stress in pathogenesis of coronary artery disease.

【背景】活性氧（reactive oxygen species， ROS）诱导的氧化应激在缺血性心脏病的发病机制中起重要作用。氧化还原状态是由抗氧化剂和ROS生成系统之间的平衡决定的。针对增强的ROS，哺乳动物细胞具有一个复杂的抗氧化酶网络，如超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶。另一方面，NAD (P) H氧化酶是血管细胞中ROS的主要来源。【目的】为了阐明氧化应激在动脉粥样硬化性血管疾病中的作用，我们采用免疫组织化学方法研究了解剖病例和定向冠状动脉粥样硬化切除术（DCA）冠状动脉标本中抗氧化酶和NAD (P) H氧化酶的表达变化。此外，采用大鼠约束模型研究慢性精神应激对氧化还原状态的影响。[结果]在非动脉粥样硬化的冠状动脉中，Cu/Zn SOD和Mn SOD在内侧平滑肌细胞（SMC）中表达，而胞质GPx （GPx-1）主要在内皮中表达，在内侧SMC中表达较弱。动脉粥样硬化斑块中迁移的SMCs和巨噬细胞大量表达这些抗氧化酶。DCA标本中ROS的产生与NADH/NADPH氧化酶p22^<phox>和氧化LDL的分布密切相关。ROS与p22^<phox>或氧化LDL的表达有相关性。慢性精神应激对大鼠抑制模型血管ROS生成的影响。[结论]抗氧化酶的表达和ROS生成系统受到动态调控。长期的精神压力导致了它们的失衡。

[Background] Oxidative stress induced by reactive oxygen species (ROS) plays an important role in pathogenesis of ischemic heart disease. The redox state is determined by the balance between antioxidants and the ROS generating system. Against enhanced ROS, mammalian cells have a complex network of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. On the other hand, NAD (P) H oxidase is a major source of ROS in vascular cells. [Purpose] To clarify the role of oxidative stress in atherosclerotic vascular diseases, we investigated by immunohistoshemistry the expressional changes of antioxidative enzymes and NAD (P) H oxidase in coronary arteries specimens obtained from autopsied cases and directional coronary atherectomy (DCA). Furthermore, the influence of chronic mental stress on the redox state was examined using rat restrain-models. [Results] In nonatherosclerotic coronary arteries, Cu/Zn SOD and Mn SOD were expressed in medial smooth muscle cells (SMC), whereas cytosolic GPx (GPx-1) was expressed mainly in endothelium and weakly in medial SMC. Migrating SMCs and macrophages in atheromatous plaques expressed these antioxidative enzymes intensively. The generation of ROS in DCA specimens were closely associated with the distribution of NADH/NADPH oxidase p22^<phox> and oxidized LDL. There was a correlation between ROS and the expression of p22^<phox> or oxidized LDL. Chronic mental stress enhanced in vascular ROS generation in rat restrain-models. [Conclusion] The expression of antioxidant enzymes and the ROS generating system are dynamically regulated. Chronic mental stress induced their imbalance.