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目的探讨基质金属原蛋白-2(MMP-2)、MMP-9、基质金属蛋白酶特异性组织抑制物-1(TIMP-1)和TIMP-2在高氧肺损伤中的作用及维甲酸(RA)的保护作用机制。方法建立高氧(FiO285%)暴露早产SD大鼠肺损伤模型,应用RT-PCR法检测MMP-2、MMP-9、TIMP-1和TIMP-2mRNA表达,采用明胶酶谱检测MMP-2和MMP-9酶原及活酶表达,采用Western blot技术检测TIMP-1和TIMP-2蛋白表达。结果与空气组比较,高氧暴露4、7、14d,MMP-2、MMP-9和TIMP-1 mRNA的表达均显著升高(P均<0.01),MMP-2活酶、MMP-9酶原及活酶和TIMP-1蛋白的表达明显上调(P<0.05);RA对空气暴露下它们的表达均无明显影响(P均>0.05),但不同程度下调高氧暴露后MMP-2、MMP-9、TIMP-1mRNA的表达和MMP-2活酶、MMP-9酶原及活酶的表达,进一步提高TIMP-1蛋白表达;高氧、RA对TIMP-2 mRNA和蛋白的表达均无明显影响(P均>0.05)。结论高氧暴露明显改变MMPs/TIMPs的表达,在肺泡形成关键时期,MMPs/TIMPs之间平衡关系的破坏是造成肺发育受阻和纤维化的重要因素;通过协调MMPs/TIMPs之间的表达,改善肺泡结构,降低肺纤维化程度,从而逆转高氧所致肺损伤,是RA发挥保护作用的重要机制之一。
Objective To investigate the effects of matrix metalloproteinase-2 (MMP-2), MMP-9, TIMP-1 and TIMP-2 on hyperoxia-induced lung injury and the effects of retinoic acid ) Protection mechanism. Methods The model of lung injury in SD rats exposed to high oxygen (FiO285%) was established. The expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA were detected by RT- The expression of TIMP-1 and TIMP-2 was detected by Western blot. Results Compared with air group, the expressions of MMP-2, MMP-9 and TIMP-1 mRNA at 4, 7, 14 d after hyperoxia exposure were significantly increased (all P <0.01) (P <0.05). RA had no significant effect on their expression under air exposure (P> 0.05), but the levels of MMP-2, MMP-9 and TIMP-1mRNA and the expression of MMP-2, MMP-9 and activity of enzymes, further improve the expression of TIMP-1 protein; The expressions of TIMP-2 mRNA and protein in hyperoxia and RA were not Obviously (P> 0.05). Conclusions Hyperoxia exposure can significantly change the expression of MMPs / TIMPs, and the destruction of the balance between MMPs / TIMPs during the critical period of alveolar formation is an important factor for the obstruction and fibrosis of lung. By coordinating the expression of MMPs / TIMPs, Alveolar structure, reduce the degree of pulmonary fibrosis, thereby reversing lung injury caused by hyperoxia, is one of the important mechanisms of RA play a protective role.