Loftus Tyler J, Thomson Andrew J, Kannan Kolenkode B, Alamo Ines G, Millar Jessica K, Plazas Jessica M, Whitley Elizabeth E, Efron Philip A, Mohr Alicia M
University of Florida Health, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA.
University of Florida, College of Medicine, Gainesville, FL, USA.
Am J Surg. 2017 Oct;214(4):610-615. doi: 10.1016/j.amjsurg.2017.06.019. Epub 2017 Jun 23.
We hypothesized that clonidine and propranolol would increase VEGF and VEGF-receptor expression and promote lung healing following severe trauma and chronic stress.
Sprague-Dawley rats were subjected to lung contusion (LC), lung contusion/hemorrhagic shock (LCHS), or lung contusion/hemorrhagic shock/daily restraint stress (LCHS/CS). Clonidine and propranolol were administered daily. On day seven, lung VEGF, VEGFR-1, VEGFR-2, and HMGB1 were assessed by PCR. Lung injury was assessed by light microscopy (*p < 0.05).
Clonidine increased VEGF expression following LCHS (43%) and LCHS/CS (46%). Clonidine increased VEGFR-1 and R-2 expression following LCHS/CS (203%* and 47%, respectively). Clonidine decreased HMGB1 and TNF-alpha expression following LCHS/CS (22% and 58%*, respectively.) Clonidine decreased inflammatory cell infiltration and total Lung Injury Score following LCHS/CS. Propranolol minimally affected VEGF and did not improve lung healing.
Clonidine increased VEGF and VEGF-receptor expression, decreased HMGB1 expression, decreased lung inflammation, and improved lung tissue repair.
我们推测可乐定和普萘洛尔会增加血管内皮生长因子(VEGF)及其受体的表达,并促进严重创伤和慢性应激后的肺愈合。
将斯普拉格-道利大鼠进行肺挫伤(LC)、肺挫伤/失血性休克(LCHS)或肺挫伤/失血性休克/每日束缚应激(LCHS/CS)处理。每天给予可乐定和普萘洛尔。在第7天,通过聚合酶链反应(PCR)评估肺组织中的VEGF、血管内皮生长因子受体-1(VEGFR-1)、血管内皮生长因子受体-2(VEGFR-2)和高迁移率族蛋白B1(HMGB1)。通过光学显微镜评估肺损伤情况(*p < 0.05)。
可乐定可增加LCHS组(增加43%)和LCHS/CS组(增加46%)的VEGF表达。可乐定可增加LCHS/CS组的VEGFR-1和VEGFR-2表达(分别增加203%和47%)。可乐定可降低LCHS/CS组的HMGB1和肿瘤坏死因子-α(TNF-α)表达(分别降低22%和58%)。可乐定可减少LCHS/CS组的炎症细胞浸润和降低肺损伤总评分。普萘洛尔对VEGF的影响极小,且未改善肺愈合情况。
可乐定可增加VEGF及其受体的表达,降低HMGB1表达,减轻肺部炎症,并改善肺组织修复。