Acikgoz Eda, Aktug Huseyin, Yigitturk Gurkan, Demir Kenan, Guven Ummu, Duzagac Fahriye, Oltulu Fatih, Yavasoglu Altug, Oktem Gulperi
1Yuzuncu Yil University, Faculty of Medicine, Department of Histology and Embryology, Van, Turkey. 2Ege University, Faculty of Medicine, Department of Histology and Embryology, Izmir, Turkey..
Folia Histochem Cytobiol. 2017;55(3):140-148. doi: 10.5603/FHC.a2017.0014. Epub 2017 Oct 10.
Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol-ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models.
An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment.
The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper-trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib.
These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway.
舒尼替尼是一种口服血管内皮生长因子抑制剂，用于治疗多种癌症。关于舒尼替尼对糖尿病影响的数据有限。在肝脏中，Notch信号通路在肝组织发育和稳态中起重要作用，其功能障碍与肝脏病理相关。本研究的目的是探讨舒尼替尼对链脲佐菌素（STZ）诱导的小鼠糖尿病肝脏的影响。
在28只雄性CD-1小鼠中建立实验性糖尿病（DM）模型。将28只雄性CD-1小鼠分为四组（每组n = 7）；对照组小鼠（C）、接受舒尼替尼治疗的对照组小鼠（C + S）、糖尿病小鼠（DM）和接受舒尼替尼治疗的糖尿病小鼠（DM + S），持续四周。通过组织化学和免疫组织化学检查肝脏的组织病理学变化。在舒尼替尼治疗后，评估对照组和糖尿病小鼠中Notch1、Jagged1、DLL-1和VEGF的免疫反应性。
肝脏中明显的形态学变化主要见于DM小鼠中肥大的肝细胞，嗜酸性颗粒数量增加；此外，一些肝细胞含有空泡样结构。DM小鼠的肝脏显示胶原纤维沉积增加。舒尼替尼治疗后，肝细胞和肝小叶的形态与对照组小鼠几乎相似。与接受舒尼替尼治疗的C、DM + S和C + S组相比，DM组肝细胞中Notch1、Jagged1、DLL-1和VEGF的免疫反应性显著降低。
这些结果表明，舒尼替尼通过抑制Notch通路有效保护肝脏免受糖尿病诱导的损伤。
