| Summary: | 博士 === 高雄醫學大學 === 牙醫學系博士班 === 106 === Oral submucous fibrosis (OSF) is an oral potentially malignant disorder and areca nut chewing is the main etiological factor of this lesion in regions with high prevalence of areca nut chewing habits. However, the molecular mechanism underlying OSF remains unknown, partly due to the lack of an appropriate animal model. The present study aims to establish and characterize two animal models of areca nut extract (ANE)-induced (1) skin fibrosis and (2) oral submucous fibrosis. In skin fibrosis model, 24 mice were equally divided into 4 groups (control, bleomycin, ANE10 and ANE20 groups) and subcutaneous (SC) injection every two days. In OSF model, 18 mice were equally divided into 3 groups (control, bleomycin and ANE 20 mg/ml groups) and subcutaneous injection was applied once every week. Six mice from each of skin group were killed via CO2 inhalation after the treatments had been administered for 3, 7, 14, and 30 days, whilst all the animals of oral groups were sacrificed after 14 and 30 days. Then, the fibrotic formation of the tissue was evaluated by histological analyses; the expression levels of the fibrotic marker proteins were assessed by immunohistochemical staining and immunoblotting. In ANE-induced skin fibrosis, ANE administration significantly increased dermal thickness and collagen deposition when compared with the control group. Moreover, ANE increased the expression of the fibrotic marker genes alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) respectively in the skin and submucous lesions. In ANE-induced OSF, ANE administration significantly increased lamina propria thickness and collagen deposition. The SC injection of ANE successfully induced skin fibrosis, exhibiting characteristics similar to those of OSF.
Moreover, these two models may facilitate future studies of the possible therapeutic method for OSF. Therefore, we tried to use two treatments: low power laser irradiation (LPLI) and forskolin (an intracellular cAMP activator). To the result showed that both treatments have therapeutic effects. However, we still need to further investigate the mechanisms of the treatments for OSF, which have indelible benefits for development of OSF clinical interventions. It is expected that the established OSF animal models are valuable to verify a potential treatment for OSF patients in the future.
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