Seese Megumi H, Steelman Andrew J, Erdman John W
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
USDA-ARS Children's Nutrition Research Center, Houston, TX, United States.
Curr Dev Nutr. 2024 Jul 14;8(8):104416. doi: 10.1016/j.cdnut.2024.104416. eCollection 2024 Aug.
To facilitate the evaluation of vitamin E (α-tocopherol, αT) status on health outcomes, the αT transfer protein knockout ( ) mouse model has proved to be an effective tool for lowering αT body stores. Our previous study showed a further reduction in grip strength in LPS-treated compared with wild-type (WT) mice during a 9-wk αT-deficient diet feeding period but did not find a difference in LPS-induced inflammatory response markers. Further optimization of this mouse model is warranted to determine the appropriate depletion period and biomarkers endpoints.
The objective was to examine whether 12 wk of an αT-deficient diet altered the inflammatory response 4 and/or 24 h after LPS injection in WT and mice.
WT and weanling littermates were fed an αT-deficient diet for 12 wk. Mice were then injected with LPS (10 μg/mouse) or saline (control) intraperitoneally and killed 4 (Study 1) or 24 h (Study 2) later. Concentrations of αT in tissues were measured via HPLC. Grip strength and burrowing were evaluated to assess sickness behaviors before/after LPS injection. Expression of genes related to inflammatory responses was examined via RT-PCR.
αT concentrations in the brain, liver, and serum of mice were notably lower or undetectable compared with WT mice in both studies. Hepatic αT concentrations were further decreased 24 h after LPS injection. Grip strength was reduced at 4 h post-injection but partially recovered to baseline values 24 h after LPS injection. The expression of genes related to inflammatory responses were altered by LPS. However, neither measure of sickness behavior nor gene expression markers differed between genotypes.
A 4-h LPS challenge reduced grip strength and resulted in an inflammatory response. At 24 h post-dosing, there was a partial, transitory recovery response in both and WT mice.
为便于评估维生素E（α-生育酚，αT）状态对健康结局的影响，αT转运蛋白敲除（ ）小鼠模型已被证明是降低αT体内储备的有效工具。我们之前的研究表明，在9周的αT缺乏饮食喂养期内，与野生型（WT）小鼠相比，LPS处理的 小鼠握力进一步下降，但未发现LPS诱导的炎症反应标志物有差异。有必要对该小鼠模型进行进一步优化，以确定合适的耗竭期和生物标志物终点。
目的是研究12周的αT缺乏饮食是否会改变WT和 小鼠在LPS注射后4小时和/或24小时的炎症反应。
将WT和 同窝断奶幼鼠喂食αT缺乏饮食12周。然后给小鼠腹腔注射LPS（10μg/小鼠）或生理盐水（对照），并在4小时（研究1）或24小时（研究2）后处死。通过HPLC测量组织中αT的浓度。评估握力和打洞行为以评估LPS注射前后的疾病行为。通过RT-PCR检测与炎症反应相关的基因表达。
在两项研究中，与WT小鼠相比， 小鼠脑、肝和血清中的αT浓度显著降低或无法检测到。LPS注射后24小时，肝脏αT浓度进一步降低。注射后4小时握力降低，但LPS注射后24小时部分恢复到基线值。LPS改变了与炎症反应相关的基因表达。然而，两种疾病行为测量指标和基因表达标志物在不同基因型之间均无差异。
4小时的LPS刺激降低了握力并导致炎症反应。给药后24小时， 和WT小鼠均出现部分短暂的恢复反应。
