Liu Zhi-Hai, Yu Ying-Qun, Li Wei-Qin, Li Jie-Shou
Research Institute of General Surgery, Nanjing University School of Medicine, Nanjing 210002, China.
Acta Pharmacol Sin. 2002 Oct;23(10):887-92.
To investigate the effects of growth hormone (GH) on NF-kappaB activity in neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide (LPS) in rats.
Male Wistar rats challenged with or without LPS (5 mg/kg) were treated with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB activities in circulating neutrophils were measured with electrophoretic mobility shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected by Western blot. Lung neutrophils sequestration and lung microvascular permeability were measured at 4 h after LPS challenge.
Circulating neutrophils in LPS challenged rats had increased NF-kappaB activity and decreased I-kappaB level as compared with controls. GH dramatically increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in neutrophils. Also, subsequently, GH treatment increased lung neutrophils sequestration and lung microvascular injury induced by LPS.
These results suggest that treatment of GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB activity and lung neutrophils sequestration are critical in vivo mechanisms mediating GH action on LPS-induced organ injury.
研究生长激素（GH）对大鼠中性粒细胞中核因子κB（NF-κB）活性以及脂多糖（LPS）诱导的中性粒细胞介导的器官损伤的影响。
对雄性Wistar大鼠给予或不给予LPS（5毫克/千克）刺激，然后用不同剂量的GH（0.5、1.0和2.0毫克/千克）处理2或4小时。采用电泳迁移率变动分析（EMSA）测定循环中性粒细胞中的NF-κB活性，通过蛋白质免疫印迹法检测循环中性粒细胞中的I-κB水平。在LPS刺激后4小时测量肺中性粒细胞滞留和肺微血管通透性。
与对照组相比，LPS刺激的大鼠循环中性粒细胞中NF-κB活性增加，I-κB水平降低。GH显著增加了LPS刺激诱导的中性粒细胞中NF-κB活性和I-κB降解。此外，随后GH治疗增加了LPS诱导的肺中性粒细胞滞留和肺微血管损伤。
这些结果表明，GH治疗对LPS诱导的器官损伤有害而非有益。中性粒细胞NF-κB活性增加和肺中性粒细胞滞留是介导GH对LPS诱导的器官损伤作用的关键体内机制。
