女性停經後因雌激素缺乏，代謝症候群與心血管疾病風險激增，已知苜蓿芽乙酸乙酯與茉莉甲醇萃物含植物性雌激素，本研究探討此兩種萃物對卵巢摘除之ApoE剔除母鼠代謝症候群與動脈粥狀硬化的影響。苦瓜乙酸乙酯萃物含PPAR活化劑，本實驗室過去發現苦瓜乙酸乙酯萃物可降低ApoE剔除公鼠的動脈粥狀硬化，本研究進一步探討此萃物對頭臂動脈斑塊穩定度與代謝症候群的影響。
實驗一、8~12週齡ApoE剔除母鼠，接受卵巢摘除或假手術後，依年齡及體重分為四組，假手術組 (Sham, n=9) 與去卵巢組 (OVX, n=12) 餵予高脂飼料(20%fat)；去卵巢苜蓿組 (OVX+A, n=12) 與去卵巢茉莉組 (OVX+J, n=11) 分別給予添加1%苜蓿芽乙酸乙酯萃物或茉莉甲醇萃物的高脂飼料，15週後犧牲。結果OVX+A組體重及心臟重量顯著低於OVX組 ( p<0.05)，腎臟重量顯著低於其他三組 ( p<0.05)；OVX+J組子宮周脂和肝臟重量顯著低於OVX組 ( p<0.05)；血液TG、FFA、glucose、insulin、adiponectin、leptin各組間無顯著差異，但OVX+A組於第8週時TC濃度低於OVX組 (p=0.061)，於第15週時顯著低於Sham組 ( p<0.05)。OVX+A組肝臟膽固醇濃度顯著低於OVX+J組及OVX組；OVX+A組及OVX+J組肝臟TG濃度顯著低於OVX組 ( p<0.05)，與肝切片脂質染色結果一致。OVX+A組及OVX+J組脂肪細胞體積顯著比OVX組小 ( p<0.05)。OVX+A組主動脈縱切脂肪堆積較其他組輕，但無顯著差異；頭臂動脈橫切新生內層及中層面積比值(I/M, intima/media ratio) OVX+A組略有降低趨勢 (p=0.063)，且下降頭臂動脈病灶處MMP-9及IL-1之免疫染色，增加TM之染色。胸主動脈促發炎因子蛋白質MMP-9及IL-1表現量則是各組無顯著差異。
實驗二、19週齡ApoE剔除公鼠依年齡及體重分為兩組，餵予高脂飼料 (20%fat) (HF, n=8)，或高脂飼料加1%山苦瓜乙酸乙酯萃物 (HF+BEA, n=9)，12週後犧牲。結果兩組間體重、組織重量及血液生化值、頭臂動脈I/M ratio皆無顯著差異。頭臂動脈免疫染色分析顯示HF+BEA組不能降低MMP-9、IL-1β表現，但可顯著增加保護因子TM及HO-1的表現。胸主動脈發炎因子IL-1β蛋白質表現量中，HF+BEA組顯著減少。
總結：於卵巢摘除之ApoE剔除母鼠，苜蓿芽乙酸乙酯萃物可顯著改善體重、腹腔脂肪細胞體積、血膽固醇、肝膽固醇及脂肪濃度，使頭臂動脈病灶處MMP-9及IL-1表現下降、TM表現增加，可能具改善代謝症候群與增進動脈硬化斑塊穩定度之效用；茉莉甲醇萃物可顯著改善腹腔與肝臟脂肪堆積，脂肪細胞體積大小。苦瓜乙酸乙酯萃物於ApoE剔除公鼠中，可增加頭臂動脈TM及HO-1的表現，下降胸主動脈IL-1β表現，對動脈硬化可能有改善效果。

The risks of metabolic syndrome and cardiovascular disease increase in postmenopausal women due to estrogen deficiency. The ethyl acetate extract (EAE) of alfalfa sprouts and the methanol extract of Jasminum have been found to contain phytoestrogens. We therefore investigated the effects of both extracts on metabolic syndrome and atherosclerosis in ovariectomized (OVX) apoE-/- mice. The bitter gourd EAE contains PPAR activator. Our previous studies have found the atherosclerosis reducing effect of bitter gourd EAE in male apoE-/- mice. This study further explored its impact on the stability of plague in brachiocephalic artery and metabolic syndrome in male apoE-/- mice.
In experiment 1, 8~12-wk-old female apoE-/- mice after ovariectomy or sham, were randomly divided into 4 groups. Sham (n = 9) and OVX groups (n =12) were fed high fat diets; OVX+A (n = 11) and OVX+J groups (n = 12) were fed high fat diets supplemented with 1% EAE of alfalfa sprouts, and 1% methanol extract of jasminum, respectively. After 15 wk of feeding, the mice were sacrificed. The results showed that the OVX + A group had significantly lower body weight and heart weight, and the OVX+J group had a significantly lower parametrial fat weight than the OVX group (p <0.05). Levels of serum TG, FFA, glucose, insulin, adiponectin were not significantly different among the four groups. The OVX + A group had lower serum TC level than OVX group (p = 0.061) at 8 week, and significantly lower level of hepatic TC than the OVX and OVX+J groups. Level of hepatic TG and size of abdominal adipocytes in the OVX+A and OVX+J groups were significantly lower than those in the OVX group. From the observation of brachiocephalic artery, the OVX+A group had a slightly lower ratio of artery intima/media area (I/M) (p = 0.063), a reduced expressions of matrix metalloproteinases-9 (MMP-9) and Interleukin-1IL-1 and an increased expression of thrombomodulin (TM) by immunohistochemical analysis. But, the protein expressions of MMP-9 and Il-1 in thoracic aorta analyzed by western blotting were not significantly different among groups.
In experiment 2, 19-wk-old apoE-/- male mice were randomly divided into 2 groups, fed the high fat (20%fat) diet (HF, n = 8) or the high fat diet supplemented with 1% EAE of bitter gourd (HF+BEA, n = 9). After 12 wk of feeding, the mice were sacrificed. No significant difference was found in body weight, blood biochemical parameters, and brachiocephalic artery I/M ratio between the two groups. HF + BEA Group significantly increased the expression of TM and
Hemoxygenase-1(HO-1), but did not affect those of MMP-9 and IL-1β in the section of brachiocephalic artery analyzed by immunohistochemical methods. In addition, the protein expression of IL-1 in thoracic aorta analyzed by western blotting was significantly lower in HF + BEA than in HF group.
To sum up, in OVX apoE-/- mice, the EAE of alfalfa sprouts can improve metabolic syndrome by reducing body weight, adipocyte size of abdominal fat, serum cholesterol, and hepatic cholesterol and triglyceride. It may also improve atherosclerosis by reducing MMP-9 and IL-1, and increasing TM expression on brachiocephalic artery. The methanol extract of jasminum can improve metabolic syndrome by reducing liver weight, hepatic triglyceride, abdominal fat pad and the adipocyte size. In male apoE-/- mice, the bitter gourd EAE may stabilize atherosclerotic plagues by increasing the expression of TM and HO-1 on brachiocephalic artery and decreasing the protein expression of Il-1 in thoracic aorta.

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