Hsi Zoe Y, Stewart Leslie A, Lloyd K C Kent, Grimsrud Kristin N
School of Veterinary Medicine, University of California, Davis, Davis, California.
Mouse Biology Program, University of California, Davis, Davis, California.
Comp Med. 2020 Apr 1;70(2):111-118. doi: 10.30802/AALAS-CM-19-000015. Epub 2020 Feb 3.
The Roux-en-Y Gastric Bypass (RYGB) mouse model is a vital tool for studying the pathophysiology of bariatric surgery and contributes greatly to research on obesity and diabetes. However, complications including postsurgical hypoglycemia can have profoundly negative effects. Unlike in humans, blood glucose (BG) is not typically managed in postoperative rodents, despite their critical role as translational models; without this management, rodents can experience hypoglycemia, potentially impairing wound healing, decreasing survivability, complicating interpretation of research data, and limiting translational utility. In this project, we sought to identify an optimal method for minimally invasive administration of dextrose in C57BL/6N ( = 16; 8 male, 8 female) mice. To do so, we characterized BG pharmacokinetic profiles after subcutaneous and oral-transmucosal (OTM) administration of dextrose. Compared with OTM dosage, the subcutaneous route provided more consistent and reliable delivery of glucose and did not cause significant adverse reactions. We then evaluated the frequency of hypoglycemic events after RYGB in C57BL/6N mice ( = 16; 8 male, 8 female) and the effects of subcutaneous dextrose supplementation on morbidity and mortality. BG measurement and behavioral pain assessment (grimace test) were performed for 3 d after surgery. Hypoglycemic (BG ≤ 60 mg/dL) animals were assigned to dose (5% dextrose SC) or no-dose treatment groups. Nearly all (87%) mice became hypoglycemic; 2 of these mice died. No significant intergroup difference in grimace score or mortality was detected. Overall, our results demonstrate that hypoglycemia is a frequent adverse event after RYGB in mice and that subcutaneous injection of dextrose is a safe and effective way to manage hypoglycemia. Further studies are necessary to optimize the intervention threshold and optimal dosage; regardless, we recommend glycemic management after RYGB surgery in mice.
Roux-en-Y胃旁路术（RYGB）小鼠模型是研究减肥手术病理生理学的重要工具，对肥胖和糖尿病研究有很大贡献。然而，包括术后低血糖在内的并发症会产生严重的负面影响。与人类不同，尽管术后啮齿动物作为转化模型具有关键作用，但它们的血糖（BG）通常在术后不进行管理；没有这种管理，啮齿动物可能会出现低血糖，这可能会损害伤口愈合、降低存活率、使研究数据的解释复杂化，并限制转化效用。在本项目中，我们试图确定在C57BL/6N（n = 16；8只雄性，8只雌性）小鼠中微创给予葡萄糖的最佳方法。为此，我们对皮下和口服黏膜（OTM）给予葡萄糖后的BG药代动力学特征进行了表征。与OTM给药相比，皮下途径提供了更一致、可靠的葡萄糖递送，且未引起明显不良反应。然后，我们评估了C57BL/6N小鼠（n = 16；8只雄性，8只雌性）RYGB术后低血糖事件的发生率以及皮下补充葡萄糖对发病率和死亡率的影响。术后3天进行BG测量和行为疼痛评估（鬼脸测试）。低血糖（BG≤60mg/dL）动物被分配到给药（5%葡萄糖皮下注射）或不给药治疗组。几乎所有（87%）小鼠都出现了低血糖；其中2只小鼠死亡。在鬼脸评分或死亡率方面未检测到显著的组间差异。总体而言，我们的结果表明，低血糖是小鼠RYGB术后常见的不良事件，皮下注射葡萄糖是管理低血糖的安全有效方法。需要进一步研究以优化干预阈值和最佳剂量；无论如何，我们建议对小鼠RYGB手术后进行血糖管理。
