Chance W T, Sheriff S, McCarter F, Ogle C
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
J Burn Care Rehabil. 2001 Mar-Apr;22(2):136-43. doi: 10.1097/00004630-200103000-00010.
Major burn trauma often leads to reduced gut barrier function, immunosuppression, and increased bacterial translocation. We hypothesized that treatments that maintain normal gut after burn trauma will also reduce immunosuppression and bacterial translocation. Recent studies suggest that treatment with glucagon-like peptide-2 (GLP-2), which is synthesized in the intestine and released after food intake, elicits mucosal hyperplasia in the small intestine of rodents and prevents parenteral nutrition-induced gut hypoplasia. Therefore, we determined whether GLP-2 would prevent loss of gut integrity after major burn trauma. Osmotic minipumps were implanted into the peritoneum of 22 adult, male, Sprague-Dawley rats to infuse saline (10 microl/hr; n = 14) or GLP-2 (1 microg/hr; n = 8). On the next day 8 saline-infused and 8 GLP-2-infused rats were subjected to a 25 sec duration 30% BSA open flame burn, with the remaining rats serving as sham-burn controls. Five days after burn, all rats were killed. Gut protein was assessed, and immunosuppression was estimated by the mitogenic response of cultured splenocytes to phytohemagglutinin, pokeweed, and concanavalin A. Bacterial translocation was determined by culturing the mesenteric lymph nodes. Although protein content was significantly decreased in the ileum of burned rats treated with saline, the burned rats treated with GLP-2 exhibited significant increases in protein levels in duodenum, jejunum. and ileum. Colon protein was not affected by GLP-2 infusion. Saline-treated burned rats also exhibited immunosuppression, as suggested by significantly decreased responses to each of the mitogens. Infusion of GLP-2 normalized the response by the burned rats to each of the mitogens. Lymph nodes taken from sham rats exhibited no colony forming units, whereas in both of the burn groups, 50% of the cultures were positive. However, more aggressive colonization may have occurred in the saline-infused burned rats as compared with the GLP-2-infused burned rats (81 +/- 63 vs 3 +/- 2 colony forming units). These results suggest that GLP-2 may stimulate gut mucosa and reduce immunosuppression in burned rats. However, there does not seem to be a statistically significant positive effect of GLP-2 on bacterial translocation. Thus, improving small intestine mucosa may increase immunity while being ineffective against bacterial translocation.
严重烧伤创伤常导致肠道屏障功能降低、免疫抑制及细菌易位增加。我们推测，在烧伤创伤后维持肠道正常功能的治疗方法也会减轻免疫抑制和细菌易位。近期研究表明，胰高血糖素样肽-2（GLP-2）在肠道合成并在进食后释放，可引起啮齿动物小肠黏膜增生，并预防肠外营养引起的肠道发育不全。因此，我们确定GLP-2是否能预防严重烧伤创伤后肠道完整性的丧失。将渗透微型泵植入22只成年雄性Sprague-Dawley大鼠的腹膜内，以输注生理盐水（10微升/小时；n = 14）或GLP-2（1微克/小时；n = 8）。次日，8只输注生理盐水和8只输注GLP-2的大鼠接受持续25秒的30%牛血清白蛋白明火烧伤，其余大鼠作为假烧伤对照。烧伤后5天，处死所有大鼠。评估肠道蛋白，通过培养的脾细胞对植物血凝素、商陆和刀豆球蛋白A的促有丝分裂反应来评估免疫抑制。通过培养肠系膜淋巴结来确定细菌易位。尽管用生理盐水治疗的烧伤大鼠回肠中的蛋白含量显著降低，但用GLP-2治疗的烧伤大鼠十二指肠、空肠和回肠中的蛋白水平显著升高。结肠蛋白不受GLP-2输注的影响。如对每种促有丝分裂原的反应显著降低所示，用生理盐水治疗的烧伤大鼠也表现出免疫抑制。输注GLP-2使烧伤大鼠对每种促有丝分裂原的反应恢复正常。取自假烧伤大鼠的淋巴结未显示菌落形成单位，而在两个烧伤组中，50%的培养物呈阳性。然而，与输注GLP-2的烧伤大鼠相比，输注生理盐水的烧伤大鼠可能发生了更严重的定植（81±63对3±2菌落形成单位）。这些结果表明，GLP-2可能刺激烧伤大鼠的肠道黏膜并减轻免疫抑制。然而，GLP-2对细菌易位似乎没有统计学上的显著积极作用。因此，改善小肠黏膜可能会增强免疫力，但对细菌易位无效。
