DeWitt R C, Wu Y, Renegar K B, King B K, Li J, Kudsk K A
Department of Surgery, University of Tennessee, Memphis 38163, USA.
Ann Surg. 2000 Jan;231(1):1-8. doi: 10.1097/00000658-200001000-00001.
To study the ability of bombesin (BBS) to recover gut-associated lymphoid tissue (GALT) and preserve immunity in a lethal model of Pseudomonas aeruginosa (Ps) pneumonia in mice receiving total parenteral nutrition (TPN).
TPN causes depression of mucosal immunity compared with enterally fed animals, which may explain the increased incidence of pneumonia in parenterally fed trauma patients. BBS prevents this TPN-induced GALT atrophy, depressed gastrointestinal and respiratory tract IgA levels, and impaired antiviral IgA-mediated mucosal immunity. The authors examined whether some supplement could be added to TPN to avoid this GALT atrophy and lower the incidence of infectious complications in the parenterally fed animal.
Male mice were randomized to chow or intravenous (IV) TPN. After 5 days of IV TPN, mice received 0, 1, 2, or 3 days of BBS IV three times a day and then were killed to harvest Peyer's patch, intraepithelium, and lamina propria for cell yields. Gastrointestinal and respiratory tract IgA levels were analyzed by enzyme-linked immunosorbent assay. Next, mice underwent intranasal inoculation with liposomes alone (nonimmune) or liposome-containing Ps polysaccharide. Ps immune mice were catheterized and randomized to chow, IV TPN, or IV TPN + BBS. The liposome group received chow but no IV catheter. These mice were given an LD90 dose of intratracheal Ps, and death rates were recorded.
GALT and gastrointestinal and respiratory tract IgA levels improved to those in chow-fed mice after 3 days of BBS. Immunization reduced the death rate from 92% in chow-fed liposome-only animals to 20% in immunized animals. TPN-fed animals lost their mucosal immunity, with a death rate of 86% compared with 21% in the TPN + BBS group.
The results demonstrate that BBS reverses TPN-induced changes in GALT and preserves mucosal immunity. Ps immunization reduces the death rate in a gram-negative pneumonia model and maintains gastrointestinal and respiratory immunity in Ps immune mice receiving IV TPN.
研究蛙皮素（BBS）在接受全胃肠外营养（TPN）的小鼠铜绿假单胞菌（Ps）致死性肺炎模型中恢复肠道相关淋巴组织（GALT）及维持免疫功能的能力。
与经肠内喂养的动物相比，TPN会导致黏膜免疫功能下降，这可能解释了经肠外喂养的创伤患者肺炎发病率增加的原因。BBS可防止TPN诱导的GALT萎缩、胃肠道和呼吸道IgA水平降低以及抗病毒IgA介导的黏膜免疫功能受损。作者研究了是否可以在TPN中添加某种补充剂以避免这种GALT萎缩，并降低经肠外喂养动物的感染并发症发生率。
将雄性小鼠随机分为正常饮食组或静脉输注（IV）TPN组。在静脉输注TPN 5天后，小鼠每天接受3次BBS静脉注射，持续0、1、2或3天，然后处死以获取派尔集合淋巴结、上皮内及固有层细胞产量。通过酶联免疫吸附测定法分析胃肠道和呼吸道IgA水平。接下来，小鼠经鼻内接种单独的脂质体（非免疫）或含Ps多糖的脂质体。对Ps免疫小鼠进行插管并随机分为正常饮食组、静脉输注TPN组或静脉输注TPN + BBS组。脂质体组给予正常饮食但不进行静脉插管。给这些小鼠气管内注射LD90剂量的Ps，并记录死亡率。
给予BBS 3天后，GALT以及胃肠道和呼吸道IgA水平恢复至正常饮食小鼠的水平。免疫接种使仅接受脂质体的正常饮食动物的死亡率从92%降至免疫动物的20%。接受TPN喂养的动物失去了黏膜免疫功能，死亡率为86%，而TPN + BBS组为21%。
结果表明，BBS可逆转TPN诱导的GALT变化并维持黏膜免疫功能。Ps免疫接种可降低革兰氏阴性肺炎模型中的死亡率，并在接受静脉输注TPN的Ps免疫小鼠中维持胃肠道和呼吸道免疫功能。
