- 學位論文
桑椹水萃物延緩第2型糖尿病引起的骨質疏鬆症
Mulberry water extract ameliorate osteoporosis in type 2 diabetes
摘要
先前文獻指出，高血糖會增加體內氧化壓力，進而併發骨質疏鬆症。根據之前研究顯示，桑椹具有良好抗氧化能力。因此，我們以高脂飲食餵食大鼠並合併以低劑量 (35 mg/kg) streptozotocin (STZ) 誘導第2型糖尿病，在給予桑椹水萃物 (MWEs) 後觀察觀察其對糖尿病併發症之影響。結果顯示，糖尿病大鼠血中鹼性磷酸酶 (ALP) 濃度明顯增加，給予MWEs九週後可有效降低ALP值。在組織病理學檢測方面，發現糖尿病大鼠脊椎骨質量明顯降低，給予MWEs可改善此情況。第1型膠原蛋白為骨骼重要的組成成分，糖尿病大鼠骨小樑中表現顯著減少，MWEs可延緩膠原蛋白表現量下降。另外，給予MWEs也可改善糖尿病引起之Runx2及第一型血色素氧化酵素 (HO-1) 表現量減少之現象。桑椹花青素 (MAEs) 為天然的類黃酮，為MWEs中重要的功能性成分之一。我們在細胞模式中以MAEs探討是否可保護高糖/油酸對小鼠成骨細胞 (MC3T3-E1) 造成的功能障礙及氧化傷害。將MC3T3-E1細胞培養於含有25 mM葡萄糖或50 μM油酸的骨誘導培養液中，並添加不同濃度的MAEs，進而檢測成骨細胞功能及氧化損傷的指標。同時處理高糖/油酸組，其ALP活性、骨結節生成及鈣離子沉積皆明顯低於單純誘導分化組。MAEs可增加ALP的表現及活性，並提升礦物化能力。綜合以上的結果顯示，MWEs/MAEs可藉由其抗氧化能力，延緩糖尿病引起的骨質疏鬆症。MWEs具有開發成之保健食品潛力，其可用來預防糖尿病併發骨疏鬆症。
並列摘要
Previous studies showed that diabetes complicated osteoporosis can be related to oxidative stress. It was documented mulberry possessed a good antioxidative ability. Thus, we developed animal models for type 2 diabetes by combination of high fat diet (HFD) fed and low-dose streptozotocin (STZ) treated rat. Herein, we used mulberry water extracts (MWEs) to feed the diabetic rat, and further to examine the potential effects. In our investigation, the level of plasma alkaline phosphatase (ALP) in diabetic rat increased significantly. After MWEs given for 9 weeks, ALP was reduced. In histological examination, we found severe bone loss in spinal bone of diabetic rat, and MWEs ameliorated the condition significantly. The collagen I, an important component existing in bone, become sparse in trabecular bone of diabetic rat, MWEs can decelerate the decrease of collagen I. Additionally, the expression of Runx2 and of heme oxygenase-1 (HO-1) reduced in diabetes were also improved as treated with MWEs. Mulberry anthocyanin extracts (MAEs), a naturally occurring flavonoid. Furthermore, we investigated to determine whether MAEs could protect osteoblasts from high glucose/ oleic acid (OA) induced dysfunction and oxidative damage in the MC3T3-E1 cells. MC3T3-E1 cells were cultured in the osteogenic medium with or without 25 mM D-Glucose, 50 μM OA or different concentration of MAEs, and markers of osteoblast function and oxidative damage were examined. Compared with differentiation incubation, high glucose/OA significantly decreased ALP activity, bone nodule generate and calcium deposition. MAEs increased cell ALP expression, ALP activity, mineralization of osteoblastic MC3T3-E1 cells in the presence of 25 mM D-Glucose and 50 μM OA. Our results demonstrate that MWEs/MAEs attenuates diabetes-complicated osteoporosis, it might be due to its antioxidative ability. Our results suggested that MWEs have the potentials to develop a functional food in diabetes to decelerate the progression of osteoporosis.