Arginase and α-smooth muscle actin induction after hyperoxic exposure in a mouse model of bronchopulmonary dysplasia.
Arginase and α-smooth muscle actin induction after hyperoxic exposure in a mouse model of bronchopulmonary dysplasia.
复制标题
支气管肺发育不良小鼠模型高氧暴露后精氨酸酶和α-平滑肌肌动蛋白的诱导。
DOI：
10.1111/1440-1681.12909
复制
发表时间：
2018
影响因子：
2.9
通讯作者：
Rogers,LynetteK
中科院分区：
文献类型：
--
作者：
Trittmann,JenniferK;Velten,Markus;Heyob,KathrynM;Almazroue,Hanadi;Jin,Yi;Nelin,LeifD;Rogers,LynetteK
L-精氨酸/NO途径是肺动脉高压的重要调节因子，是早产儿、支气管肺发育不良等慢性肺部疾病患者死亡的主要原因。L-精氨酸可被一氧化氮合酶代谢生成L-瓜氨酸和一种有效的血管扩张剂--一氧化氮。或者，L-精氨酸可以被精氨酸酶代谢成尿素和L-鸟氨酸，后者是胶原和脯氨酸形成的前体，在血管重塑中起重要作用。在目前的研究中，我们假设C3H/HEN小鼠暴露在长时间的高氧中会增加精氨酸酶的表达和肺血管壁细胞的增殖。C3H/HEN小鼠暴露于85%氧气或室内空气及肺组织匀浆14天后，用免疫印迹法检测精氨酸酶I、精氨酸酶II、内皮型一氧化氮合酶、鸟氨酸脱羧酶、鸟氨酸转氨酶和α-平滑肌肌动蛋白(α-SMA)的蛋白水平。高氧不改变精氨酸酶I或eNOS蛋白水平。然而，暴露在高氧环境中的精氨酸酶II蛋白水平是暴露在室内空气中的肺部的15倍。在高氧暴露后，肺中ODC和OAT的蛋白质水平高于室内空气中的动物。α-SMA蛋白水平在高氧暴露的肺中被发现比在室内空气中的肺高7倍。高氧暴露组肺组织α-SMA免疫组织化学染色显示肺血管壁细胞增殖明显高于室内空气肺。综上所述，这些数据与更具增殖性的血管表型是一致的，并且可能解释了支气管肺发育不良患者发展为肺动脉高压的倾向。
The L‐arginine/NO pathway is an important regulator of pulmonary hypertension, the leading cause of mortality in patients with the chronic lung disease of prematurity, bronchopulmonary dysplasia. L‐arginine can be metabolized by NO synthase (NOS) to form L‐citrulline and NO, a potent vasodilator. Alternatively, L‐arginine can be metabolized by arginase to form urea and L‐ornithine, a precursor to collagen and proline formation important in vascular remodelling. In the current study, we hypothesized that C3H/HeN mice exposed to prolonged hyperoxia would have increased arginase expression and pulmonary vascular wall cell proliferation. C3H/HeN mice were exposed to 14 days of 85% O2or room air and lung homogenates analyzed by western blot for protein levels of arginase I, arginase II, endothelial NOS (eNOS), ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and α‐smooth muscle actin (α‐SMA). Hyperoxia did not change arginase I or eNOS protein levels. However, arginase II protein levels were 15‐fold greater after hyperoxia exposure than in lungs exposed to room air. Greater protein levels of ODC and OAT were found in lungs following hyperoxic exposure than in room air animals. α‐SMA protein levels were found to be 7‐fold greater in the hyperoxia exposed lungs than in room air lungs. In the hyperoxia exposed lungs there was evidence of greater pulmonary vascular wall cell proliferation by α‐SMA immunohistochemistry than in room air lungs. Taken together, these data are consistent with a more proliferative vascular phenotype, and may explain the propensity of patients with bronchopulmonary dysplasia to develop pulmonary hypertension.