Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Japan,
Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
Pathobiology. 2021;88(3):234-241. doi: 10.1159/000512639. Epub 2021 Feb 8.
Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment.
Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase-mediated dUTP nick-end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture.
In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2'-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death.
These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.
2 型糖尿病（T2DM）与多种系统性血管症状和口干有关。据认为，高血糖引起的多尿和脱水导致身体水分减少，导致唾液分泌减少，最终导致口干。在 T2DM 中，活性氧（ROS）的产生增加会导致血管内皮细胞和包括胰腺和角膜在内的上皮组织受损。因此，在高血糖环境中，类似的现象可能发生在其他组织和腺体中。
使用 T2DM 模型小鼠（db/db）检查唾液腺组织损伤。通过末端转移酶介导的 dUTP 缺口末端标记（TUNEL）评估组织损伤。测量丙二醛（MDA）和 8-羟基-2'-脱氧鸟苷的水平，以及 Bax/Bcl-2 比值作为氧化应激的指标。此外，通过在高糖条件下培养来自小鼠唾液腺的正常细胞，评估体外 ROS 产生和细胞损伤。
体内和体外分析表明，db/db 小鼠唾液腺组织中 TUNEL 阳性细胞的百分比更高，MDA 和 8-羟基-2'-脱氧鸟苷的水平也更高。这表明高血糖诱导的氧化应激损伤了与唾液分泌相关的脂质和 DNA。为了分析高血糖促进 ROS 产生的机制，分离了来自小鼠唾液腺的细胞。用高糖培养基培养的细胞增强了 ROS 的产生，并促进了细胞凋亡和坏死。
这些发现提示了一种新的机制，即高血糖诱导的 ROS 产生促进了唾液腺损伤，导致唾液分泌减少。
