全反式维甲酸对COPD大鼠肺组织中基质金属蛋白酶-2,9表达的影响

Effect of All-trans Retinoic Acid on Expression of Matrix Metalloproteinases in Lung Tissue of COPD Rat

目的:探讨MMP-2,MMP-9及TIMP-1在肺损伤和修复过程中的作用及全反式维甲酸(ATRA)拮抗COPD的机制。方法:100只健康雄性SD大鼠被随机分为4组:正常对照组、模型组、ATRA预防组、ATRA治疗组。采用烟熏加内毒素致大鼠COPD模型,观察病理组织形态学改变,应用免疫组化检测肺组织中MMP及TIMP的表达,及ATRA对它们的影响。结果:正常肺组织MMP-2、MMP-9、TIMP-1有少量染色阳性,模型组比正常对照组表达明显增强。ATRA预防和治疗组比模型组表达明显下降,但仍比正常对照组增高。结论:MMP-2、MMP-9表达增强,使细胞外降解增加,可能是肺气肿形成机制之一。ATRA可以降低COPD大鼠的MMP-2和MMP-9表达。

Objective：To explore the effect of MMP-2, MMP-9 and TIMP-1 in rat model with COPD and effect and mechanism of all-trans retinoic acid on COPD. Methods： Hundred healthy male SD rats were randomly divided into 4 groups： normal control group, COPD model group, all-trans retinoic acid （ATRA） prophylactic group, and ATRA treated group. COPD rat models were established by intratrached instillation of LPS and exposure to smoke. Expression of MMP and TIMP were detected by immunohistochemical method and effect of ATRA were observed. Results： MMP-2, MMP-9 and TIMP-1 in normal lung tissue were slightly positive. Expressions of MMP-2, 9 and TIMP-1 were significantly higher in COPD group than those in normal control group. Expression was significantly decreased in both two ATRA groups than that in COPD model group, but still higher than that of normal control group, Conclusion： Elevated MMP-2 and MMP-9 may increase the excelluar degradation, and contribute to the development of emphysema, ATRA may decrease expressions of MMP-2 and MMP-9 in rats with COPD.