环氧合酶-2与核因子-κB在人动脉粥样硬化病变中的表达及机制探讨

【目的】了解环氧合酶-2与核因子-κB在人动脉粥样硬化病变不同阶段的表达和相关性以及环氧合酶-2可能通过核因子-κB途径促进动脉粥样硬化病变的进程。【方法】用免疫组化法检测环氧合酶-2与核因子-κB在动脉粥样硬化不同阶段中的细胞定位及阳性面积百分比。在培养的人脐动脉平滑肌细胞中，用逆转录聚合酶链法和细胞免疫化学染色法检测核因子-κB特异性阻断剂PDTC作用后血管紧张素Ⅱ诱导的环氧合酶-2 mRNA和蛋白的表达。【结果】环氧合酶-2与核因子-κB可见于AS病变中的巨噬细胞、平滑肌细胞和内皮细胞，在斑块肩部尤明显；早期和晚期病变环氧合酶-2与核因子-κB的阳性面积百分比均明显高于正常（P〈0．05），晚期病变表达最高；晚期病变中易损斑块环氧合酶-2与核因子-κB的表达又明显高于稳定斑块；二者的表达存在相关性（r=0.296，P〈0．05）；在细胞实验中，PDTC可明显阻断血管紧张素Ⅱ诱导的人血管平滑肌细胞中环氧合酶-2 mRNA和蛋白的表达（P〈0．05）。【结论】环氧合酶-2参与动脉粥样硬化病变过程，而这一过程至少部分由核因子-κB途径介导；环氧合酶-2抑制剂与核因子-κB阻断剂均可能成为治疗动脉粥样硬化的新方法。

Coexpression of cyclo-oxygenase 2 and nuclear factor-kappa B in human atherosclerotic lesions and exploration of the mechanism

[Objective] To observe the expression and correlation of cyclo-oxygenase-2 （COX-2） and Nuclear factor- kappa B （NF-κB） in different human atherosclerotic lesions, and the probability of COX-2 in promoting atherosclerosis by NF-κB pathway. [Methods] Immunohistochemical techniques were used for localization and defermination the percentages of positive area of COX-2 and NF-κB proteins in different stages of human atherosclerotic lesions, and RT-PCR and cell immunocytochemical technique were used for mRNA and protein analysis of COX-2 induced by angiotensin- Ⅱ with PDTC which is the specific inhibitor of NF-κB in cultured human umbilical artery smooth muscle cells. [Results] COX- 2 was found in macrophages, some smooth muscle cells and endothelial cells in atherosclerotic lesions, especially in the shoulder region of the plaques. The percentages of positive area of COX-2 and NF-κB in early and late stage lesions were significantly higher than those in normal （ P 〈 0.05）, which in late stage lesions were the highest. Simultaneously the expressions of COX-2 and NF-κB were notably higher in vulnerable plaques than those in stable plaques, and correlated （r = 0. 296）. The study in cultured cells suggested that PDTC could downregulate mRNA and protein of COX-2 induced by angiotensin-Ⅱ （ P 〈 0.05）. [Conclusions] COX-2 may be involved in the pathogenesis of atherosclerosis, which is mediated at lest in part, by NF-κB pathway. Both COX-2 antagonists and NF-κB inhibitors renresent a novel theraneuticapproach to the treatment of atherosclerosis.