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抗血管内皮生长因子抗体的应用恢复了 2 型糖尿病小鼠模型的唾液分泌功能。

Application of anti-vascular endothelial growth factor antibody restores the function of saliva secretion in a type 2 diabetes mouse model.

机构信息

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.

出版信息

J Oral Biosci. 2024 Sep;66(3):619-627. doi: 10.1016/j.job.2024.06.011. Epub 2024 Jun 27.

Abstract

OBJECTIVES

Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes.

METHODS

Male KK-A mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 μg/kg) 24 h before the experiment.

RESULTS

Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1β were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group.

CONCLUSION

Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.

摘要

目的

口干症是 2 型糖尿病的常见并发症,会增加龋齿、吞咽困难和味觉障碍的风险。虽然抗血管内皮生长因子(VEGF)抗体,如雷珠单抗(RBZ),已被用于治疗糖尿病性视网膜病变,但它们对唾液腺的影响尚不清楚。本研究评估了 RBZ 对唾液腺的作用,以减少炎症并恢复 2 型糖尿病小鼠模型的唾液功能。

方法

使用雄性 KK-A 小鼠作为 2 型糖尿病模型(10-12 周龄)。糖尿病(DM)组接受磷酸盐缓冲液,而 DM+RBZ 组在实验前 24 小时接受 RBZ(100μg/kg)腹腔内给药。

结果

体外灌流实验显示,DM+RBZ 组下颌下腺(SMG)的唾液分泌明显增加。此外,该组 TNF-α 和 IL-1β 的 mRNA 表达水平显著降低。相比之下,定量反转录 PCR 显示,DM+RBZ 组的水通道蛋白 5 表达水平显著升高。此外,SMG 中的淋巴细胞浸润点数量在 DM+RBZ 组明显减少。最后,DM+RBZ 组的腺泡细胞内钙信号明显高于 DM 组。

结论

用 RBZ 治疗 2 型糖尿病小鼠模型可通过其抗炎作用恢复唾液分泌。

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