姜黄素防治慢性低O_2高CO_2大鼠肺动脉高压与c-Jun、c-Fos的关系研究

Effect of curcumin on pulmonary arterial pressure and c-Jun, c-Fos in chronic hypoxic hypercapnic rats

目的：研究姜黄素对慢性低O_2高CO_2大鼠肺动脉高压及肺动脉管壁c-Jun和c-Fos表达的影响。方法：36只SD大鼠随机分为正常对照组、低O_2高CO_2组、低O_2高CO_2+姜黄素组(简称姜黄组)。采用图像分析、免疫组化和组织原位杂交技术等方法观察姜黄素对慢性低O_2高CO_2大鼠肺动脉压力、血管显微结构及肺动脉管壁原癌基因c-Jun和c-Fos表达影响。结果：血流动力学检测显示姜黄素组mPAP较低O_2高CO_2组明显降低(P＜0．01)，组间mCAP比较差异无显著性。光镜下姜黄素组肺细小动脉内弹力板扭曲、中膜平滑肌细胞增生及管腔狭窄程度均明显轻于低O_2高CO_2组。电镜下姜黄素组大鼠肺细小动脉内皮细胞结构基本正常，中膜平滑肌细胞增生较轻，胶原少见；外膜胶原纤维较低O_2高CO_2大鼠明显减少。免疫组化法发现肺细小动脉c-Jun和c-Fos平均吸光度值低O_2高CO_2组明显高于正常对照组(P＜0．01)，姜黄素组明显低于低O_2高CO_2组(P＜0．01)；原位杂交法显示肺细小动脉管壁c-Jun mRNA平均吸光度值姜黄素组显著低于低O_2高CO_2组(P＜0．01)。结论：姜黄素有抑制慢性低O_2高CO_2性肺动脉高压和改善肺血管结构重建的作用，下调c-Fos、c-Jun及其基因的表达，抑制血管平滑肌细胞的增殖可能是其重要作用机制。

AIM： To investigate the effect of curcurain on pulmonary arterial pressure and the expression of c-Jun and c-Fos in chronic hypoxia hypercapnia rats. METHODS： SD rats were randomly divided into normal control group （NC）, hypoxic hypercapnic group （HH）, hypoxic hypercapnia ＋ curcumin group （HC）. c-Fos, c-Jun and their mRNA were observed in pulmonary arterioles of rats by the technique of immunohistochemistry and in situ hybridization. RESULTS： Hemodynamics showed that mPAP was markedly lower in group HC than that in group HH （ P 〈 0.01 ）. Differences of mCAP were not significant in three groups. Light microscopy showed media thickness of pulmonary arterioles was markedly higher in group HH than that in group NC, and vessel cavity turned more strait in group HH than that in group NC. However, the damage of pulmonary arterioles in group HC was significantly slighter than that of group HH. Electron microscopy showed that structure of the endothelial cells in pulmonary arterioles in group HC was near to normal, and the proliferation of medial smooth muscle cells and collagen fibers in adventitia is markedly lighter than those of group HH. Expression of c-Jun and c-Fos in pulmonary arterioles were significantly higher in group HH than those of NC group （P 〈 0.01）, and they were lower in group HC than those of group HH （P 〈 0.01 ）. In situ hybridization showed that c-Jun mRNA in pulmonary arterioles was significantly lower in rats of group HC than that in group HH. CONCLUSION： Curcumin can inhibit hypoxic hypercapnic pulmonary hypertension and pulmonary vessel remodeling, and it may be a vital mechanism of curcumin to decrease the expression of c-Jun, c-Fos and to inhibit the proliferation of medial smooth muscle cells.