Department of Surgery, Section of Pediatric Surgery, Yale School of Medicine, New Haven, Connecticut.
Department of Surgery, Section of Pediatric Surgery, Yale School of Medicine, New Haven, Connecticut.
J Surg Res. 2019 Apr;236:326-331. doi: 10.1016/j.jss.2018.11.033. Epub 2019 Jan 3.
Parenterally administered selective serotonin reuptake inhibitors, such as citalopram, increase intestinal mucosal absorptive surface by day 7 of treatment. We hypothesized that enteral citalopram would also induce intestinal mucosal growth, thus allowing for therapy with an oral agent.
Following a habituation period, C57BL/6 mice received peanut butter pellets containing 10, 50, or 100 mg/kg/d citalopram for 7 d (n = 5); or 25 mg/kg/d citalopram for 14 (n = 3) or 21 (n = 5) d; or plain peanut butter pellets for 7 (n = 2), 14 (n = 2), or 21 d (n = 3). Two-centimeter ileal segments were harvested and prepared for microscopic assessment of villus height (VH), crypt depth, villus width (VW), and crypt width. Mucosal surface area (MSA) was calculated and data were compared using Student's t-test.
Enteral administration of citalopram had virtually no effect on VH, VW, or crypt depth after 7 d; crypt width decreased significantly (P value range 0.0002 to <0.0001), likely contributing to the increases in MSA (P value range 0.0578 to 0.0006). After 14 d of treatment, citalopram significantly increased VH (P < 0.0001), VW (P = 0.0058), and ileal MSA per mm (P = 0.0007). The increase in MSA was sustained at 21 d (P < 0.0001).
Enteral citalopram given for 14 d results in increased VH and ileal MSA, which remains increased by day 21. Selective serotonin reuptake inhibitors show potential as oral therapy for serious intestinal disorders such as short bowel syndrome.
肠内给予选择性 5-羟色胺再摄取抑制剂(如西酞普兰),在治疗的第 7 天可增加肠道黏膜的吸收表面积。我们假设肠内给予西酞普兰也会诱导肠道黏膜生长,从而可以使用口服药物进行治疗。
在适应期后,C57BL/6 小鼠接受含有 10、50 或 100mg/kg/d 西酞普兰的花生酱丸剂治疗 7 天(n=5);或给予 25mg/kg/d 西酞普兰治疗 14 天(n=3)或 21 天(n=5);或给予普通花生酱丸剂治疗 7 天(n=2)、14 天(n=2)或 21 天(n=3)。采集 2cm 的回肠段并准备进行绒毛高度(VH)、隐窝深度、绒毛宽度(VW)和隐窝宽度的显微镜评估。计算黏膜表面积(MSA),并使用学生 t 检验比较数据。
肠内给予西酞普兰在 7 天内几乎对 VH、VW 或隐窝深度没有影响;隐窝宽度显著减小(P 值范围 0.0002 至 <0.0001),可能导致 MSA 增加(P 值范围 0.0578 至 0.0006)。治疗 14 天后,西酞普兰显著增加 VH(P<0.0001)、VW(P=0.0058)和每毫米回肠 MSA(P=0.0007)。21 天时 MSA 的增加仍然持续(P<0.0001)。
肠内给予西酞普兰治疗 14 天可导致 VH 和回肠 MSA 增加,第 21 天仍持续增加。选择性 5-羟色胺再摄取抑制剂显示出作为严重肠道疾病(如短肠综合征)的口服治疗的潜力。