Alavi K, Prasad R, Lundgren K, Schwartz M Z
Department of Surgery, Alfred I duPont Hospital for Children, Wilmington, DE 19803, USA.
J Pediatr Surg. 2000 Feb;35(2):371-4. doi: 10.1016/s0022-3468(00)90043-5.
BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR.
Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM.
IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d.
In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.
背景/目的：最近研究显示，白细胞介素-11（IL-11）可增加大鼠广泛小肠切除术后（MSBR）的肠黏膜质量。然而，肠黏膜质量增加可能与底物吸收增加无关。本研究旨在探讨MSBR后全身给予不同剂量IL-11对小肠吸收功能和黏膜质量的影响。
25只Sprague-Dawley大鼠接受80%小肠切除及空肠回肠端端吻合术。术后7天，所有大鼠均植入颈静脉导管并连接皮下渗透泵。根据泵内所含物质将大鼠分为5组：第1组（对照组，n = 5）给予0.1%牛血清白蛋白（BSA），第2至5组（每组n = 5）分别给予250、500、750和1000μg/kg/d的IL-11。经过14天的输注期后，采用体内封闭循环技术测量[14C]半乳糖和[14C]甘氨酸的吸收情况。同时测定每组的黏膜DNA含量。采用方差分析进行统计学分析，结果以平均值±标准误表示。
先前研究中使用的250μg/kg/d剂量的IL-11对底物吸收无显著影响。然而，与对照组相比，给予更高剂量的IL-11可使底物吸收和黏膜质量显著增加。基于所测参数（半乳糖吸收，比对照组增加72%；甘氨酸吸收，比对照组增加112%；DNA含量，比对照组增加98%）产生总体最佳反应的IL-11剂量为750μg/kg/d。
这些数据首次表明，除增加黏膜质量外，IL-11还能增强MSBR后超出正常适应性反应的吸收功能。此外，IL-11对吸收功能的最大作用在750μg/kg/d时出现，这是先前报道研究中所用剂量的3倍。本研究提示IL-11在肠道功能不全患者的临床治疗中可能具有应用价值。
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