| 摘要: | 停經後雌激素的缺乏使骨質流失顯著增加，同時也會增加肌肉流失。Insulin-Like Growth Factor (IGF)-1活化PI3K / Akt / mTOR訊息傳遞路徑，可促進肌肉合成；另一方面，肌肉生長抑制素(myostatin)透過降低Akt磷酸化之訊號路徑，而增加atrogin-1和MuRF1萎縮因子的表現，而增加肌肉的萎縮。停經後的肥胖也可能導致IGF-1下降，而導致PI3K /Akt / mTOR訊號路徑活性降低，蛋白質合成減少、蛋白質分解增加，進而導致肌肉萎縮。不論是骨質密度下降或是肌肉流失，均會影響高齡者的行動能力。米糠(rice bran, RB)是碾米的副產物富含蛋白質、膳食纖維和酚類化合物，可降低發炎反應、具有改善胰島素敏感性等作用，而發酵米糠(fermented rice bran, FRB)經由Aspergillus kawachii發酵後，與米糠相比，更增加了GABA、Tryptophan等生物活性成分，可能有助於減少肌肉的合成及降低骨質流失，改善行動能力。因此，本研究之動機是以卵巢切除動物模式模擬停經狀況，介入不同劑量的發酵米糠水萃物(1%和5% FRB)，以了解發酵米糠水萃物是否可透過調節骨質代謝速率以及肌肉生合成萎縮路徑，減緩骨質流失及減少肌肉萎縮，以維持行動力。實驗設計，以24週齡Sprague-Dawley(SD)雌性大鼠32隻，有8隻為假手術組，其餘每組為8隻，分別是卵巢切除控制組(OVX- control, OVXC)；卵巢切除1%發酵米糠水萃物(OVX- fermented rice bran extract 1 %, OVX 1%)；卵巢切除5%發酵米糠水萃物(OVX- fermented rice bran extract 5%, OVX5%)，介入12週後犧牲，收集血液、肌肉、股骨等進一步分析。結果顯示OVX1%與OVX 5%組，相對握力高於OVXC組。OVX 1%與OVX 5%組血漿AST(aspartate amino transferase)、ALT(alanine amino transferase)顯著低於OVXC組。OVX1%與OVX 5%組血漿alkaline phosphatase(ALP)顯著低於OVXC組。血漿pyridinoline (PYD) OVX 1%組顯著低於OVXC組。血漿tartrate-resistant acid phosphatase(TRAP) OVX 5%組顯著低於OVXC組。遠端股骨骨質密度，OVX 1%與OVX 5%顯著高於OVXC組。遠端股骨骨小樑數量(trabecular number, Tb.N)，OVX 5%與OVX 1%組顯著高於OVXC組。腓腸肌單位肌肉面積，OVXC 5%組顯著高於OVXC組。肌肉促萎縮因子Atrogin-1，OVX 1%組顯著低於OVXC組。肌肉促合成因子mTOR，OVX 5%顯著高於OVXC組。綜合上述介入發酵米糠水萃物可以降低OVX後的骨分解標誌物及骨質密度流失，可以提升OVX大鼠相對握力以及減少肌肉萎縮。
The lack of estrogen after menopause significantly increases bone loss and also increases muscle loss. Muscle protein synthesis can be regulated by activating the PI3K / Akt / mTOR pathway through insulin-like growth factor (IGF)-1 stimulation. On the other hand, myostatin activates atrogin-1 and MuRF1 expression resulting in muscle degradation. Postmenopausal obesity may also lead to downregulating IGF-1, resulting in the inactivation of the PI3K /Akt /mTOR signaling pathway and decreased muscle protein synthesis. No matter the bone density mass decrease or muscle atrophy, it may reduce elderly action ability. Rice bran (RB) is a by-product of rice milling, rich in protein, dietary fiber, and phenolic compounds, which can reduce inflammation and improve insulin sensitivity. Compared to rice bran fermented by Aspergillus kawachii, fermented rice bran(FRB) has more bioactive components such as GABA and tryptophan, which may help reduce muscle synthesis and bone loss and improve physical activity. Therefore, in this study, an ovariectomized animal model was used to simulate menopausal conditions, and treat with different doses of FRB water extract (1% and 5% FRB), to understand whether fermented rice bran water extract can regulate bone metabolism and muscle synthesis and atrophy pathways, thereby slowing down bone loss and muscle atrophy. Thirty-two 24-week-old Sprague-Dawley (SD) female rats, eight rats assigned into the sham group (Sham), and twenty-four rats underwent bilateral ovariectomy (ovariectomy, OVX). The groups were as follows: sham group; ovariectomy control group (OVXC); OVX-1% FRB water extract (OVX 1%); OVX-5% FRB water extract (OVX 5%). After 12 weeks of intervention, the blood, skeleton muscle and femur bone were collected. The results show that the relative forelimb grip strengths of the OVX1% and OVX5% groups were higher than those of the OVXC group. The plasma AST and ALT in OVX1% and OVX5% groups were significantly lower than those in the OVXC group. Compared to the OVXC group, the plasma ALP levels in OVX1% and OVX5% groups were significantly decreased. The plasma PYD level in the OVX1% group was significantly lower than the OVXC group. The plasma TRAP level in the OVX5% group was significantly lower than the OVXC group. Distal femur bone density in the OVX5% group was significantly higher than the OVXC group. Trabecular number (Tb.N), in the OVX1% and OVX5% groups, were significantly higher than those in the OVXC group. The muscle area of the gastrocnemius by cross-section is significantly higher in the OVXC5% group than in the OVXC group. Furthermore, the OVX 5% group had a higher mTOR, and OVX 1% group had a lower atrogin1 protein expression than those in the OVXC group. In conclusion, fermented rice bran water extract can retain more femur bone density by reducing bone decomposition markers, and decrease muscle atrophy by increasing muscle strength, enhancing muscle synthesis, and reducing muscle degradation in this OVX rat model. |
