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目的探讨MMP-9(基质金属蛋白酶-9)和TIMP-1(基质金属蛋白酶抑制物-1)在高氧致CLD新生大鼠肺组织中的动态变化和在Ⅳ型胶原重塑中的作用。方法足月新生大鼠在生后12h内分别持续吸入浓度为0.90～0.95的高氧和空气,于1,3,7,14和21d,应用免疫组化的方法分别检测肺组织MMP-9和TIMP-1蛋白表达的动态变化,同时采用ELISA法动态检测肺组织中Ⅳ型胶原蛋白含量。结果MMP-9在高氧3d时的表达较空气组增强,蛋白平均灰度值为:(126.23±6.95)vs(130.38±7.36),P<0.05,其余时间点两组比较差异无显著性;TIMP-1在3d后高氧组肺组织的表达均高于空气组,3d和7d时平均灰度值为:(126.22±6.49)vs(129.49±4.75),(119.70±7.33)vs(124.99±6.83)(P<0.05),14d和21d差异有显著性,值为(112.35±10.29)vs(120.08±7.77),(109.19±10.56)vs(118.22±6.32)(P<0.01);高氧组ColⅣ含量在14d[(24.78±5.42)vs(14.90±2.44),P<0.05]和21d[(40.27±1.94)vs(26.13±1.94),P<0.01]均高于空气组。结论新生大鼠随着吸入高氧时间的延长,MMP-9/TIMP-1的平衡状态遭到破坏,Ⅳ型胶原降解失衡,促进了早期基膜损伤的加重和晚期伴有Ⅳ型胶原沉积的肺纤维化。
Objective To investigate the dynamic changes of MMP-9 and TIMP-1 in the lung tissue of neonatal rats with hyperoxia-induced CLD and their roles in collagen remodeling. Methods Full-term neonatal rats were exposed to hyperoxia and air at a concentration of 0.90-0.95 within 12 hours after birth. The levels of MMP-9 and IL-6 in lung tissues were detected by immunohistochemistry on day 1,3,7,14 and 21, respectively TIMP-1 protein expression in the dynamic changes, while the dynamic detection of collagen type Ⅳ collagen content in lung tissue by ELISA. Results The expression of MMP-9 in hyperoxia group was higher than that in air group. The average gray value of MMP-9 protein was (126.23 ± 6.95) vs (130.38 ± 7.36), P <0.05. There was no significant difference between the two groups at other time points. The expression of TIMP-1 in the hyperoxia group was higher than that in the air group after 3d, and the average gray values at the 3d and 7d were (126.22 ± 6.49) vs (129.49 ± 4.75), (119.70 ± 7.33) vs (124.99 ± (P <0.01). Compared with the control group (P <0.05), the difference was significant on the 14th and 21st day (112.35 ± 10.29 vs 120.08 ± 7.77, 109.19 ± 10.56 vs 118.22 ± 6.32, P <0.01) Col Ⅳ content was significantly higher in air group than those in air group at 14 days [(24.78 ± 5.42) vs (14.90 ± 2.44), P <0.05] and 21 days (40.27 ± 1.94 vs 26.13 ± 1.94, P <0.01) Conclusions The equilibrium state of MMP-9 / TIMP-1 is destroyed with the prolongation of hyperoxia exposure in neonatal rats, and the imbalance of type IV collagen is imbalanced, which promotes the increase of early basement membrane injury and the late deposition of type IV collagen Pulmonary Fibrosis.