Jeschke Marc G, Herndon David N, Finnerty Celeste C, Bolder Ullrich, Thompson James C, Mueller Ulla, Wolf Steven E, Przkora Rene
Shriners Hospital for Children and Department of Surgery, University Texas Medical Branch, Galveston, Texas 77550, USA.
J Surg Res. 2005 Aug;127(2):183-9. doi: 10.1016/j.jss.2005.02.008. Epub 2005 Apr 14.
Gut mucosal integrity and function is impaired after severe trauma with associated increases in small bowel epithelial cell apoptosis and decreases in cell proliferation. Growth hormone improves gastrointestinal function during chemotherapy and has anabolic effects on protein synthesis. The purpose of this study was to determine whether growth hormone can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur.
Rats were pair-fed, given a thermal trauma, and received saline (n = 28) or GH (2.5 mg/kg every 24 h, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, apoptotic, and proliferative mediators, such as Caspases-3, -8, Fas and Fas-Ligand, Bcl-2, and Bcl-x. In addition serum cytokines were determined.
Gut epithelial cell apoptosis and proliferation were increased in both groups after the thermal injury (P < 0.05). GH had neither an effect on small bowel epithelial cell apoptosis or proliferation, nor dependent cellular mediators after thermal injury. However, GH significantly improved villous morphology (height and cell number) when compared with controls (P < 0.05). RhGH was found to significantly increase serum TNF-alpha compared to controls (P < 0.05).
Growth hormone improves small bowel homeostasis after severe trauma independent from small bowel epithelial cell apoptosis or proliferation, probably by increasing the life span.
严重创伤后肠道黏膜完整性和功能受损,伴有小肠上皮细胞凋亡增加和细胞增殖减少。生长激素在化疗期间可改善胃肠功能,并对蛋白质合成具有合成代谢作用。本研究的目的是确定生长激素是否能改善损伤后的小肠内环境稳定,以及这些变化通过何种细胞机制发生。
将大鼠配对饲养,给予热损伤,然后分别给予生理盐水(n = 28)或生长激素(每24小时2.5 mg/kg,n = 28)。在损伤后1、2、5和7天采集小肠和血清。检测指标包括黏膜凋亡、增殖、绒毛形态、凋亡和增殖介质,如半胱天冬酶-3、-8、Fas和Fas配体、Bcl-2和Bcl-x。此外,还测定血清细胞因子。
热损伤后两组的肠道上皮细胞凋亡和增殖均增加(P < 0.05)。生长激素对热损伤后的小肠上皮细胞凋亡或增殖以及相关细胞介质均无影响。然而,与对照组相比,生长激素显著改善了绒毛形态(高度和细胞数量)(P < 0.05)。与对照组相比,重组人生长激素显著增加血清肿瘤坏死因子-α(P < 0.05)。
生长激素可改善严重创伤后的小肠内环境稳定,与小肠上皮细胞凋亡或增殖无关,可能是通过延长寿命实现的。