Barta Bence Pál, Onhausz Benita, Egyed-Kolumbán Abigél, Al Doghmi Afnan, Balázs János, Szalai Zita, Ferencz Ágnes, Hermesz Edit, Bagyánszki Mária, Bódi Nikolett
Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary.
Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary.
Biomedicines. 2024 Oct 15;12(10):2347. doi: 10.3390/biomedicines12102347.
BACKGROUND/OBJECTIVES: Type 1 diabetes affects cytokines as potential inducers of NFκB signalling involved in inflammation and neuronal survival. Our goal was to assess the expression of NFκB p65 and its negative regulator, Nrf2, in myenteric neurons and adjacent smooth muscle of different gut segments after chronic hyperglycaemia and immediate insulin treatment.
After ten weeks of hyperglycaemia, intestinal samples of control, streptozotocin-induced diabetic and insulin-treated diabetic rats were prepared for fluorescent immunohistochemistry, immunogold electron microscopy, ELISA and qPCR.
In the diabetic rats, the proportion of NFκB p65-immunoreactive myenteric neurons decreased significantly in the duodenum and increased in the ileum. The density of NFκB p65-labelling gold particles increased in the ileal but remained unchanged in the duodenal ganglia. Meanwhile, both total and nuclear Nrf2 density increased in the myenteric neurons of the diabetic duodenum. In smooth muscle, NFκB p65 and Nrf2 density increased in the small intestine of diabetic rats. While on the mRNA level, NFκB p65 and Nrf2 were induced, on the protein level, NFκB p65 increased and Nrf2 decreased in muscle/myenteric plexus homogenates. Insulin treatment had protective effects.
Our findings reveal a segment-specific NFκB and Nrf expression in myenteric neurons and ganglionic muscular environments, which may contribute to regional neuronal survival and motility disturbances in diabetes.
背景/目的：1型糖尿病会影响细胞因子，而细胞因子是参与炎症和神经元存活的NFκB信号通路的潜在诱导剂。我们的目标是评估慢性高血糖和立即进行胰岛素治疗后，不同肠段的肌间神经元和相邻平滑肌中NFκB p65及其负调节因子Nrf2的表达情况。
在高血糖状态持续十周后，将对照大鼠、链脲佐菌素诱导的糖尿病大鼠以及接受胰岛素治疗的糖尿病大鼠的肠道样本用于荧光免疫组织化学、免疫金电子显微镜、酶联免疫吸附测定和定量聚合酶链反应。
在糖尿病大鼠中，十二指肠中NFκB p65免疫反应性肌间神经元的比例显著降低，而回肠中则增加。回肠神经节中NFκB p65标记金颗粒的密度增加，而十二指肠神经节中则保持不变。与此同时，糖尿病十二指肠肌间神经元中总Nrf2和核Nrf2密度均增加。在平滑肌中，糖尿病大鼠小肠中NFκB p65和Nrf2密度增加。在mRNA水平上，NFκB p65和Nrf2被诱导，而在蛋白水平上，肌肉/肌间神经丛匀浆中NFκB p65增加而Nrf2减少。胰岛素治疗具有保护作用。
我们的研究结果揭示了肌间神经元和神经节肌肉环境中存在节段特异性的NFκB和Nrf表达，这可能导致糖尿病中局部神经元存活和运动障碍。
