D-galactose로 유도된 타액 분비 저하 노화 랫드 모델에서 GLP-1 수용체 작용제 Exendin-4를 이용한 항염증 및 타액 분비 개선 = Amelioration of Hyposalivation in D-galactose-Induced Aging Mimic Rat Model by the GLP-1 Receptor Agonist, Exendin-4

다국어 초록 (Multilingual Abstract)

Xerostomia is commonly associated with aging, diabetes, and other systemic conditions. It disrupts oral homeostasis and consequently elevates the likelihood of dental caries, periodontal disorders, and oral infections. Accordingly, mitigating xerostomia is expected to help prevent these oral pathologies and improve patients’ quality of life. Because rodents cannot report subjective sensations of oral dryness, experimentally induced hyposalivation is used as an appropriate surrogate to study underlying mechanisms and potential interventions. Exendin-4 is a GLP-1 receptor agonist initially discovered in the saliva of Heloderma suspectum. It was developed as an antidiabetic medication. Using a D-galactose-based aging model in rats, this study explored the capacity of Exendin-4 to restore salivary secretion. An experimental model of hyposalivation resembling aging was created by giving rats D-galactose (300 mg/kg, intraperitoneally) each day for 7 weeks. Thereafter, Exendin-4 was provided for 2 weeks at two dosage levels (0.5 and 1 µg/head). We evaluated improvements by measuring salivary flow rates and conducting various histological and biochemical analyses. Exendin-4 treatment significantly reversed the age-related decline in salivary secretion and preserved the typical morphological characteristics of acinar cells. Histochemical staining indicated that both acidic and neutral mucin accumulation were reduced, and TUNEL analysis revealed a decrease in apoptotic cells in the salivary gland. In summary, Exendin-4 exhibits beneficial effects on D-galactose–induced hyposalivation by improving salivary secretion, preserving glandular structure, decreasing apoptotic cell death, and restoring the expression of AQP-5 and the GLP-1 receptor in the submandibular gland. Therefore, this study suggests that Exendin-4 may be considered a potential therapeutic candidate for age-related hyposalivation.

목차 (Table of Contents)

• 1. INTRODUCTION 1
• 2. MATERIALS AND METHODS 3
• 2.1 Animals 3
• 2.2 Collection of Saliva 4
• 2.3 Histopathological Examination 4
• 2.4 Apoptosis Analysis 5
• 2.5 Immunohistochemistry (IHC) 5
• 2.6 Measurement of GLP-1 6
• 2.7 Total Protein Quantification 6
• 2.8 Statistical Analysis 6
• 3. RESULTS 7
• 3.1. Evaluation of salivary secretion in the D-galactose aging mimic model and its restoration by Exendin-4 7
• 3.2 The role of Exendin-4 in mitigating D-galactose-induced histological alterations in submandibular glands 9
• 3.3 The role of Exendin-4 in reducing acidic and neutral mucin accumulation in the submandibular glands 11
• 3.4 The role of Exendin-4 in restoring diminished AQP-5 and GLP-1 receptor expression in the submandibular glands 13
• 3.5 The role of Exendin-4 in reducing inflammation and D-galactose-induced apoptosis in the submandibular glands 15
• 4. DISCUSSION 18
• 5. CONCLUSION 23
• 6. REFERENCES 24
• 국문초록 30
• ACKNOWLEDGEMENT 32