抗生素治疗对囊性纤维化小鼠脂肪吸收的影响。
Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis.
机构信息
Department of Pediatrics, Beatrix Children's Hospital-University Medical Center Groningen, Groningen, The Netherlands.
出版信息
Pediatr Res. 2012 Jan;71(1):4-12. doi: 10.1038/pr.2011.4.
INTRODUCTION
Improving fat absorption remains a challenge in cystic fibrosis (CF). Antibiotics (AB) treatment has been shown to improve body weight in CF mice. The mechanism may include improvement in fat absorption. We aimed to determine the effect of AB on fat absorption in two CF mouse models.
RESULTS
AB did not improve total fat absorption. Interestingly, AB accelerated the absorption of isotope-labeled fats, in both Δ/Δ and WT mice. The changes observed were not related to the solubilization capacity of bile or to changes in the bacteria in the small intestine. AB reduced the fecal excretion of cholate by ~50% (P < 0.05) in both CF mouse models, indicating improved intestinal bile salt absorption.
DISCUSSION
In conclusion, AB treatment does not improve total fat absorption in CF mice but does decrease fecal loss of bile salts and accelerate long-chain fatty acid (LCFA) absorption.
METHODS
For 3 weeks, we administered oral AB (ciprofloxacin/metronidazole) or control treatment to homozygous ΔF508 (Δ/Δ), cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-), and wild-type (WT) mice and quantified fat absorption using a 72-h fat balance test. In Δ/Δ mice, we assessed fat absorption kinetics by administering tri-1-(13)C-palmitin and 1-(13)C-stearate intragastrically and determining the appearance of stable isotope-labeled fats in plasma. We quantified biliary and fecal bile salts (gas chromatography) and small intestinal bacteria (quantitative-PCR).
简介
提高脂肪吸收能力仍然是囊性纤维化（CF）的一个挑战。抗生素（AB）治疗已被证明可改善 CF 小鼠的体重。其机制可能包括改善脂肪吸收。我们旨在确定 AB 对两种 CF 小鼠模型中脂肪吸收的影响。
结果
AB 并未改善总脂肪吸收。有趣的是，AB 加速了 Δ/Δ 和 WT 小鼠中同位素标记脂肪的吸收。观察到的变化与胆汁的溶解能力或小肠内细菌的变化无关。AB 减少了 CF 小鼠模型中胆酸盐的粪便排泄量约 50%（P < 0.05），表明改善了肠道胆盐吸收。
讨论
总之，AB 治疗并未改善 CF 小鼠的总脂肪吸收，但可减少胆汁盐的粪便丢失并加速长链脂肪酸（LCFA）的吸收。
方法
我们对纯合子 ΔF508（Δ/Δ）、囊性纤维化跨膜电导调节因子（CFTR）敲除（-/-）和野生型（WT）小鼠进行了 3 周的口服 AB（环丙沙星/甲硝唑）或对照治疗，并使用 72 小时脂肪平衡试验量化了脂肪吸收。在 Δ/Δ 小鼠中，我们通过胃内给予三-1-（13）C-棕榈酸和 1-（13）C-硬脂酸，并确定稳定同位素标记脂肪在血浆中的出现来评估脂肪吸收动力学。我们量化了胆汁和粪便中的胆汁盐（气相色谱法）和小肠细菌（定量 PCR）。
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