在肠内和肠外喂养条件下BALB/c与C57BL/6小鼠对创伤的固有黏膜免疫系统反应

　　背景：与人类相似，正常进食的远交系小鼠在创伤后气道和肠道免疫球蛋白A（IgA）有所增加。肠外营养（PN）可消除以上两部位IgA增加的效应。有关近交系小鼠的免疫学特性需要更详细的研究；然而，尚无可用于这种研究的特异性品系。虽然BALB/c和C57BL/6均是常见的近交系小鼠，但两者对类似应激的免疫应答却存在差异。本文着重研究能最佳复制远交系小鼠和人类对损伤进行免疫应答的近交系小鼠。

　　方法：进食或PN共5天，然后在手术创伤后0或8h时处死（BALB/c：n=16～21/组；C57BL/6：n=12～15/组）。对支气管肺泡灌洗（BAL）液通过酶联免疫吸附试验分析IgA、肿瘤坏死因子（TNF）-α、白介素（IL）-1β、IL-6，同时对小肠灌洗液（SIWF）中的IgA进行分析。

　　结果：进食或PN的BALB/c小鼠在创伤后尽管BAL中的TNF-α和SIWF中的IgA有所增加（进食：264±28比548±37，P＜0.0001；PN：150±12比301±17，P＜0.0001），但BAL中的IgA无显著增加（进食：P=0.1；PN：P=0.7）。进食喂养的C57BL/6在创伤后黏膜IgA（BAL：149±33比342±87，P=0.01；SIWF：236±28比335±32，P=0.006）和BAL细胞因子显著增加。PN组C57BL/6在创伤后的BALIgA（P=0.9），BAL细胞因子、SIWF的IgA（P=0.1）均无显著改变。

　　结论：C57BL/6小鼠对创伤的应答反应与远交系小鼠和人类相似，从而为研究创伤后黏膜免疫反应提供了合适的模型。BALB/c小鼠对创伤的黏膜免疫反应存在差异，不能作为研究人类创伤后反应的复制模型。

JPEN J Parenter Enteral Nutr. 2016;40(2):256-63.

Innate Mucosal Immune System Response of BALB/c vs C57BL/6 Mice to Injury in the Setting of Enteral and Parenteral Feeding.

Busch RA, Jonker MA, Pierre JF, Heneghan AF, Kudsk KA.

Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Department of Medicine-Gastroenterology, University of Chicago, Chicago, Illinois; Veterans Administration Surgical Services, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.

BACKGROUND: Outbred mice exhibit increased airway and intestinal immunoglobulin A (IgA) following injury when fed normal chow, consistent with humans. Parenteral nutrition (PN) eliminates IgA increases at both sites. Inbred mice are needed for detailed immunological studies; however, specific strains have not been evaluated for this purpose. BALB/c and C57BL/6 are common inbred mouse strains but demonstrate divergent immune responses to analogous stress. This study addressed which inbred mouse strain best replicates the outbred mouse and human immune response to injury.

METHODS: Intravenously cannulated mice received chow or PN for 5 days and then underwent sacrifice at 0 or 8 hours following controlled surgical injury (BALB/c: n = 16-21/group; C57BL/6: n = 12-15/group). Bronchoalveolar lavage (BAL) was analyzed by enzyme-linked immunosorbent assay for IgA, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, while small intestinal wash fluid (SIWF) was analyzed for IgA.

RESULTS: No significant increase in BAL IgA occurred following injury in chow- or PN-fed BALB/c mice (chow: P = .1; PN: P = .7) despite significant increases in BAL TNF-α and SIWF IgA (chow: 264 ± 28 vs 548 ± 37, P < .0001; PN: 150 ± 12 vs 301 ± 17, P < .0001). Injury significantly increased mucosal IgA in chow-fed C57BL/6 mice (BAL: 149 ± 33 vs 342 ± 87, P = .01; SIWF: 236 ± 28 vs 335 ± 32, P = .006) and BAL cytokines. After injury, PN-fed C57BL/6 mice exhibited no difference in BAL IgA (P = .9), BAL cytokines, or SIWF IgA (P = .1).

CONCLUSIONS: C57BL/6 mice exhibit similar airway responses to injury as outbred mice and humans, providing an appropriate model for studying mucosal responses to injury. The BALB/c mucosal immune system responds differently to injury and does not replicate the human injury response.

KEYWORDS: cytokines; immunonutrition; nutrition; parenteral nutrition; research and diseases; trauma

PMID: 25403938

PMCID: PMC4433866

DOI: 10.1177/0148607114558489