Department of Surgery, Section of Pediatric Surgery at Yale University, New Haven, CT.
Department of Surgery, Section of Pediatric Surgery at Yale University, New Haven, CT.
J Pediatr Surg. 2019 Jun;54(6):1245-1249. doi: 10.1016/j.jpedsurg.2019.02.027. Epub 2019 Mar 1.
Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption.
Wild-type C57Bl/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) FL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage. Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05.
Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage.
Potentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure.
肠内的血清素会影响肠道的稳态，并充当黏膜生长因子。此前，我们发现血清素再摄取转运蛋白（SERT）缺陷型小鼠的黏膜表面积增加，隐窝细胞增殖增强。因此，我们假设血清素介导的黏膜生长也会导致碳水化合物和脂质吸收增强。
将野生型 C57Bl/6（WT）和 SERT 敲除（SERTKO）小鼠禁食后，用 D-木糖或硼二吡咯甲川（BODIPY）FL-C12 中链脂肪酸类似物进行灌胃。从灌胃后 30 至 360 分钟从血液中连续测量血清 D-木糖和 BODIPY 浓度。从两组小鼠中采集小肠用于比较形态计量学参数。绘制图表的曲线下面积进行计算，平均值与学生 t 检验进行比较，显著性水平为 p<0.05。
与 WT 相比，SERTKO 动物的中肠和远段小肠的绒毛高度和隐窝深度明显更大。与 WT 相比，SERTKO 动物的 D-木糖和 BODIPY 整体吸收量更大。SERTKO 动物的 D-木糖吸收持续升高，而 BODIPY 吸收最初延迟，然后在灌胃后 60-360 分钟时，SERTKO 动物的吸收持续且显著增加。
SERTKO 小鼠中血清素信号的增强导致小肠黏膜生长，并在体内增强碳水化合物和脂肪的吸收。这些功能的增加支持了靶向血清素信号系统以增强肠道衰竭时肠道适应的概念。
