雄性 Goto-Kakizaki 大鼠的小肠重塑。
Small intestine remodeling in male Goto-Kakizaki rats.
机构信息
Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil.
Department of Medical Clinic, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
出版信息
Physiol Rep. 2021 Feb;9(3):e14755. doi: 10.14814/phy2.14755.
BACKGROUND
Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model.
METHODS
Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals.
KEY RESULTS
We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1β concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1β reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls.
CONCLUSIONS
The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
背景
肥胖与胰岛素抵抗（IR）和 2 型糖尿病（T2DM）的发展有关；然而，并非所有 T2DM 患者都肥胖。Goto-Kakizaki（GK）大鼠是自发性非肥胖 2 型糖尿病的实验模型。有证据表明，肠道有助于 GK 动物的 IR 发展。这一信息促使我们研究这种动物模型的小肠重塑。
方法
本研究使用 4 月龄雄性 Wistar（对照）和 GK 大鼠。切除小肠后，分离十二指肠、近端空肠和回肠。然后，我们测量了两组动物小肠段的绒毛和肌层及黏膜层组织形态学、杯状细胞丰度、全肌间和黏膜下神经元群体以及炎症标志物的表达，并测量了肠道转运。
主要结果
我们发现，GK 大鼠的肠道面积减小（p<0.0001），十二指肠（p=0.01）和回肠（p<0.0001）的隐窝深度减小，空肠（p<0.0001）的隐窝深度增加，空肠和回肠的绒毛更长（p<0.0001），十二指肠（p<0.01）和回肠（p<0.0001）的绒毛更厚，十二指肠、空肠和回肠的肌层更厚（p<0.0001），十二指肠和空肠的 IL-1β浓度升高（p<0.05），十二指肠、空肠和回肠的 NF-κB p65 浓度升高（p<0.05）。我们观察到实验组肌层、肌间神经元和神经胶质细胞中 IL-1β反应性增加。GK 大鼠还表现出空肠和回肠黏膜下神经元密度显著降低，所有研究肠段的神经节肥大（p<0.0001），与对照组相比，肠道转运明显减慢（约 25%）。
结论
GK 大鼠的 IR 和 T2DM 发展与小肠重塑有关，包括小肠形态学的显著改变、局部炎症和肠道转运减少。
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