Thakker-Varia S, Tozzi C A, Poiani G J, Babiarz J P, Tatem L, Wilson F J, Riley D J
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
Am J Physiol. 1998 Aug;275(2):L398-406. doi: 10.1152/ajplung.1998.275.2.L398.
Exposure of rats to hypoxia causes pulmonary arterial remodeling, which is partly reversible after return to air. We hypothesized that degradation of excess collagen in remodeled pulmonary arteries in the posthypoxic period is mediated by endogenous matrix metalloproteinases (MMPs). Total proteolytic, collagenolytic, and gelatinolytic activities, levels of stromelysin-1 and tissue inhibitor of metalloprotease-1 (TIMP-1), and immunolocalization of stromelysin-1 in main pulmonary arteries were determined after exposure of rats to 10% O2 for 10 days followed by normoxia. We observed transient increases in total proteolytic, collagenolytic, and gelatinolytic activities and expression of approximately 72-, 68-, and 60-kDa gelatinases by zymography within 3 days of cessation of hypoxic exposure. The level of TIMP-1 increased as the stromelysin-1 level increased. Immunoreactive stromelysin-1 was localized predominantly in the luminal region of normal and hypertensive pulmonary arteries. These results are consistent with the notion that endogenous MMPs may mediate the breakdown of excess collagen in remodeled pulmonary arteries during the early posthypoxic period.
将大鼠置于低氧环境会导致肺动脉重塑，回到正常空气环境后这种重塑部分是可逆的。我们推测，低氧后时期重塑肺动脉中过量胶原蛋白的降解是由内源性基质金属蛋白酶（MMPs）介导的。在大鼠暴露于10%氧气环境10天然后恢复常氧后，测定了主肺动脉中的总蛋白水解活性、胶原水解活性和明胶水解活性、基质溶解素-1水平和金属蛋白酶组织抑制剂-1（TIMP-1）水平，以及基质溶解素-1的免疫定位。我们观察到，在低氧暴露停止后的3天内，通过酶谱法检测到总蛋白水解活性、胶原水解活性和明胶水解活性以及约72 kDa、68 kDa和60 kDa明胶酶的表达出现短暂增加。TIMP-1水平随着基质溶解素-1水平的升高而升高。免疫反应性基质溶解素-1主要定位于正常和高血压肺动脉的管腔区域。这些结果与内源性MMPs可能在低氧后早期介导重塑肺动脉中过量胶原蛋白分解的观点一致。
