Busch Rebecca A, Heneghan Aaron F, Pierre Joseph F, Neuman Joshua C, Reimer Claire A, Wang Xinying, Kimple Michelle E, Kudsk Kenneth A
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Veteran Administration Surgical Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
JPEN J Parenter Enteral Nutr. 2016 Sep;40(7):1042-9. doi: 10.1177/0148607115585353. Epub 2015 May 1.
Parenteral nutrition (PN) increases the risk of infection in critically ill patients and is associated with defects in gastrointestinal innate immunity. Goblet cells produce mucosal defense compounds, including mucin (principally MUC2), trefoil factor 3 (TFF3), and resistin-like molecule β (RELMβ). Bombesin (BBS), a gastrin-releasing peptide analogue, experimentally reverses PN-induced defects in Paneth cell innate immunity. We hypothesized that PN reduces goblet cell product expression and PN+BBS would reverse these PN-induced defects.
Two days after intravenous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 15), PN (n = 13), or PN+BBS (15 µg tid) (n = 12) diets for 5 days. Defined segments of ileum and luminal fluid were analyzed for MUC2, TFF3, and RELMβ by quantitative reverse transcriptase polymerase chain reaction and Western blot. Th2 cytokines interleukin (IL)-4 and IL-13 were measured by enzyme-linked immunosorbent assay.
Compared with chow, PN significantly reduced MUC2 in ileum (P < .01) and luminal fluid (P = .01). BBS supplementation did not improve ileal or luminal MUC2 compared with PN (P > .3). Compared with chow, PN significantly reduced TFF3 in ileum (P < .02) and luminal fluid (P < .01). BBS addition did not improve ileal or luminal TFF3 compared with PN (P > .3). Compared with chow, PN significantly reduced ileal RELMβ (P < .01). BBS supplementation significantly increased ileal RELMβ to levels similar to chow (P < .03 vs PN; P > .6 vs chow). Th2 cytokines were decreased with PN and returned to chow levels with BBS.
PN significantly impairs the goblet cell component of innate mucosal immunity. BBS only preserves goblet cell RELMβ during PN but not other goblet cell products measured.
肠外营养（PN）会增加重症患者的感染风险，且与胃肠道固有免疫缺陷有关。杯状细胞产生黏膜防御化合物，包括黏蛋白（主要是MUC2）、三叶因子3（TFF3）和抵抗素样分子β（RELMβ）。蛙皮素（BBS）是一种胃泌素释放肽类似物，实验表明其可逆转PN诱导的潘氏细胞固有免疫缺陷。我们推测PN会降低杯状细胞产物的表达，而PN+BBS可逆转这些由PN诱导的缺陷。
静脉插管两天后，将雄性癌症研究所小鼠随机分为三组，分别给予普通饲料（n = 15）、PN（n = 13）或PN+BBS（15μg，每日三次）（n = 12）饮食，持续5天。通过定量逆转录聚合酶链反应和蛋白质印迹法分析回肠和肠腔液特定节段中的MUC2、TFF3和RELMβ。通过酶联免疫吸附测定法测量Th2细胞因子白细胞介素（IL）-4和IL-13。
与普通饲料组相比，PN显著降低了回肠（P <.01）和肠腔液（P =.01）中的MUC2。与PN组相比，补充BBS并未改善回肠或肠腔中的MUC2（P >.3）。与普通饲料组相比，PN显著降低了回肠（P <.02）和肠腔液（P <.01）中的TFF3。与PN组相比，添加BBS并未改善回肠或肠腔中的TFF3（P >.3）。与普通饲料组相比，PN显著降低了回肠中的RELMβ（P <.01）。补充BBS可使回肠中的RELMβ显著增加至与普通饲料组相似的水平（与PN组相比，P <.03；与普通饲料组相比，P >.6）。PN会降低Th2细胞因子水平，而BBS可使其恢复至普通饲料组水平。
PN显著损害固有黏膜免疫中的杯状细胞成分。BBS仅在PN期间保留杯状细胞的RELMβ，但对所检测的其他杯状细胞产物无此作用。
