Diabetes can lead to dysfunction of the secretory capacity in salivary glands. Activation of the receptor for advanced glycation end products (RAGE) and its ligands has been suggested to participate in chronic disorders such as diabetes and its complications. In this study, the expression of RAGE, high mobility group box 1 (HMGB1) and advanced glycation end products (AGE), as well as the effects of low-power laser irradiation (LPLI) in salivary glands of diabetic rats were evaluated, and the mechanisms involved were characterized. The expression of RAGE and HMGB1 at the protein and mRNA levels was observed in submandibular glands (SMGs) of streptozotocin-induced diabetic rats. A diode laser was applied at 660 nm, 70 mW, 20 J/cm2, 0.56 J/point, with a spot area of 0.028 cm2 and its in vivo effects and the pathways involved were evaluated. Immunohistochemistry and western blotting analysis were performed for inflammatory and apoptosis markers. Diabetes up-regulates HMGB1/AGE/RAGE axis gene expression in SMGs that is associated with activation of the nuclear factor kappa B (NF-κB) pathway. Interestingly, LPLI suppresses NF-κB activation induced by inflammation. LPLI also reduces diabetes-induced apoptosis. That effect was accompanied by decreased levels of Bax, and cleaved caspase 3, which were up-regulated in diabetes. Taken together, our data suggest that LPLI reduces diabetes-induced inflammation by reducing the induction of HMGB1, ultimately leading to inhibition of apoptosis in submandibular glands of diabetic rats.
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机译:糖尿病会导致唾液腺分泌功能障碍。已建议晚期糖基化终产物(RAGE)的受体及其配体的激活参与慢性疾病,例如糖尿病及其并发症。在这项研究中,评估了糖尿病大鼠唾液腺中RAGE,高迁移率族盒1(HMGB1)和高级糖基化终产物(AGE)的表达以及低功率激光照射(LPLI)的作用,并描述了所涉及的机制。在链脲佐菌素诱导的糖尿病大鼠的下颌下腺(SMG)中观察到RAGE和HMGB1在蛋白质和mRNA水平的表达。施加了660 nm,70 mW,20 J / cm 2 sup>,0.56 J /点的二极管激光器,光斑面积为0.028 cm 2 sup>及其体内效应并评估了所涉及的途径。免疫组织化学和蛋白质印迹分析进行了炎症和凋亡标记。糖尿病会上调SMG中的HMGB1 / AGE / RAGE轴基因表达,这与核因子κB(NF-κB)途径的激活有关。有趣的是,LPLI抑制炎症诱导的NF-κB活化。 LPLI还减少了糖尿病引起的细胞凋亡。这种作用伴随着Bax水平的降低和caspase 3的切割,在糖尿病中它们被上调。两者合计,我们的数据表明LPLI通过减少HMGB1的诱导来减少糖尿病引起的炎症,最终导致糖尿病大鼠下颌下腺细胞凋亡的抑制。
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