利用切除卵巢鼠之動物模式探討紅麴山藥對於停經後骨質疏鬆症之影響

Abstract

本實驗利用切除卵巢鼠作為模擬停經後婦女的動物模式，分別利用不同劑量的山藥與紅麴山藥，及以大豆異黃酮做為正控制組分別餵食大鼠，觀察大鼠骨質的變化情況。Citrinin、monacolin K、monascin 及 ankaflavinc 的濃度分別為4.63 ppm、104.8 ppm、369 ppm、602.8 ppm。山藥及紅麴山藥不含異黃酮類及木質酚類植物雌激素，但皆含薯蕷皂苷配基 (diosgenin)，在紅麴山藥及山藥的含量分別為 1.36 mg/g 及 0.68 mg/g。進行手術前後利用微型電腦斷層儀 (microcomputed tomography, micro-CT) 及雙能量 X 射線吸收儀 (dual energy x-ray absorptiometry, DEXA) 測定骨質狀況，結果顯示手術前各組骨質無明顯的差異，手術三個月後即誘導出骨質疏鬆症。接下來餵食樣品四週後，由 micro-CT 影像定量結果可知，各組的骨質狀況相對於 OVX 組皆有改善，尤以餵食紅麴山藥組 I. RMD 2X、II. RMD 2X、II. RMD 2X 最為顯著。餵食大豆異黃酮組 (ISO) 之骨鹼性磷酸酶 (bone alkaline phosphatase, bone-ALP) 活性有較高的趨勢，而本實驗餵食的樣本 (山藥與紅麴山藥) 對於大鼠之活性無顯著的影響。由骨鈣素濃度測定結果可知，除了 I. dioscorea 1X 組之外，其餘各組之骨質合成作用相對於 OVX 組皆有改善。右股骨進行 micro-CT 3 D 影像分析結果中，觀察出試驗組各組與 OVX 組比較，骨質皆有正向的改善，尤以 ISO、I. RMD 2X、II. RMD 2X 三組改善最為顯著。右股骨遠端骨小樑定量的結果中，餵食異黃酮組與餵食兩倍劑量的紅麴山藥組，骨質相較於 OVX 組有改善的趨勢，其中骨小樑厚度之分析結果具有顯著差異。在肝、腎血清指標及染色切片的安全性評估中，除了因切除卵巢引起的脂肪堆積，造成少數輕微至中度脂肪肝的情況之外，其他指標與檢驗皆為正常。

This experiment established the ovariectomized rat model of postmenopausal osteoporosis and used different dosage of dioscorea and red mold dioscorea as well as soy isoflavone as positive control to study the changing in rats’ bones.The concentrations of citrinin, monacolin K, monascin, and ankaflavinc in red mold dioscorea were 4.63 ppm, 104.8 ppm, 369 ppm, and 602.8 ppm, respectively. No phytoestrogens were found in neither red mold dioscorea nor dioscorea, except for diosgenin. The concentrations of diosgenin in red mold dioscorea and dioscorea were 1.36 mg/g and 0.68 mg/g, respectively. Before and after operation, micro-CT (microcomputed tomography) and DEXA (dual energy x-ray absorptiometry) were used to measure the bone mass condition. Resluts showed that bone conditions had no significant difference among groups before operation and osteoporosis was induced after operation for three months. After feeding sampes for four weeks, the bone mass conditions of each group were improved in comparison with OVX group by the quantification of micro-CT images. I. RMD 2X、II. RMD 2X、II. RMD 2X these three groups showed remarkable improvement.The bone-ALP (bone alkaline phosphatase) activity was higher in the soy isoflavone feeded group (ISO) and other experimental groups feeded red mold dioscorea and dioscorea showed no significant influence in bone-ALP activity. In the analyzing results of osteocalcin concetrations, each group had better bone-formation condition than OVX group, except for I. dioscorea 1X. With micro-CT 3 D images each experimental group has positive changes of bone mass condition in comparison with OVX group, especially ISO、I. RMD 2X、II. RMD 2X these three groups. By the quantification of right distall femurs’ trabecular bones, ISO、I. RMD 2X、II. RMD 2X theses groups showed positive changes of bone mass condition in comparison with OVX group and showed statistically significance in the analyzing results of trabecular thickness. As to iver and kidney index in serum and histopathological examination, every index and examination were normal except for a few slight to moderate fatty change in livers causing by ovariectomized-induced fatty accumulation.