Liu Zhihai, Yu Yingqun, Jiang Yun, Li Jieshou
Department of Surgery, Nanjing University College of Medicine, China.
Ann Clin Lab Sci. 2002 Spring;32(2):164-70.
The purpose of this study was to examine the effects of growth hormone (GH) on nuclear factor kappa B (NF-kappaB) activation and organ injury induced by lipopolysaccharide (LPS) in rats. Male Wistar rats were divided into 6 groups treated with saline, LPS (5 mg/kg), LPS plus GH (0.5, 1.0, 2.0 mg/kg), or GH (2.0 mg/kg) alone for 2 or 4 hr. NF-kappaB activity and I-kappaB level in lung, lung accumulation of neutrophils, and lung microvascular injury were measured. LPS-challenged rats had increased NF-kappaB activity and decreased I-kappaB level in lung, compared to controls. GH dramatically enhanced NF-kappaB activation and I-kappaB degradation induced by LPS challenge. LPS plus GH treatment increased lung accumulation of neutrophils, compared with LPS treatment. Also, subsequently, GH treatment increased lung microvascular injury induced by LPS. These findings suggest that treatment with GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased NF-kappaB activation may be a critical in vivo mechanism that mediates GH action on LPS-induced organ injury. Thus, it is appropriate to rethink GH administration in critical illnesses; further studies are required to evaluate the safety and clinical benefits of GH administration in such conditions.
本研究旨在探讨生长激素（GH）对脂多糖（LPS）诱导的大鼠核因子κB（NF-κB）激活及器官损伤的影响。将雄性Wistar大鼠分为6组，分别用生理盐水、LPS（5 mg/kg）、LPS加GH（0.5、1.0、2.0 mg/kg）或单独使用GH（2.0 mg/kg）处理2或4小时。检测肺组织中NF-κB活性、I-κB水平、中性粒细胞在肺中的聚集以及肺微血管损伤情况。与对照组相比，LPS刺激的大鼠肺组织中NF-κB活性增加，I-κB水平降低。GH显著增强了LPS刺激诱导的NF-κB激活和I-κB降解。与LPS处理组相比，LPS加GH处理组增加了肺组织中中性粒细胞的聚集。此外，随后GH处理增加了LPS诱导的肺微血管损伤。这些发现表明，GH治疗对LPS诱导的器官损伤有害而非有益。NF-κB激活增加可能是介导GH对LPS诱导的器官损伤作用的关键体内机制。因此，有必要重新思考危重病中GH的应用；需要进一步研究来评估在此类情况下GH应用的安全性和临床益处。
