臺灣博碩士論文加值系統

梅 (Prunus mume Sieb. et Zucc.) 為薔薇科之落葉喬木，在中國傳統醫藥中具鎮咳、祛痰、止吐和解熱之功效。已知其具有多種生理活性，包含抗肥胖、抗氧化、抗骨質疏鬆、降血糖、抗疲勞與抗癌等作用。梅精為梅果實之濃縮萃取物，但由於製程需長時間加熱會破壞機能性成分，進而降低其生理功效。因此，本研究將利用複方結合方式，以梅精為基底並外加不同比例之梅果、黑蒜和仙草萃取物，形成 7 種梅精複方。利用高脂/膽固醇飲食誘導倉鼠高血脂模式，進一步評估樣品之降血脂潛力。內容分為兩部分：(一) 以高脂/膽固醇飲食誘導倉鼠高血脂進行不同梅精複方之篩選 (動物預實驗)；(二) 不同劑量梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之改善效應 (動物主實驗)。在動物預實驗之結果得知，梅精複方 4 能降低血清三酸甘油酯、總膽固醇和 LDL-C 之含量，亦具有減少肝臟總脂質堆積並促進糞便膽固醇排出之效用。由此結果顯示，梅精複方 4 為最能有效改善高血脂之複方。在動物主實驗之結果得知，給予高血脂倉鼠梅精複方 4 (100 mg/kg b.w.) 後，可顯著降低血清中三酸甘油酯、總膽固醇及丙二醛含量。同時，亦能有效減少肝臟總脂質與三酸甘油酯堆積並促進糞便總脂質之排出。進一步探討高血脂倉鼠之肝臟組織基因表現，梅精複方 4 不僅可提升 LXR α、ABCG5、ABCA1 與 CYP51 表現，還能抑制 ACC、FAS、DGAT-2、HMG-CoA reductase、SREBP-1a 與 SREBP-1c 表現。此外，其可改善高血脂倉鼠之腸道菌群豐富度及多樣性，增加 Lactobacillus acidophilus、Bifidobacterium animalis 及減少 Helicobacter pylori 數量，並透過促進膽固醇代謝及抑制其合成，而可能具有改善高血脂之效果。綜合上述結果得知，梅精複方 4 具有改善高脂/膽固醇飲食誘導倉鼠血脂異常之功效，未來可進一步開發成為具有調節血脂質功效之健康食品。

Prunus mume Sieb. et Zucc. is the deciduous tree of the Rosaceae family. It has antitussive, expectorant, antiemetic, and antipyretic effects in Chinese traditional medicine. It provides many physiological activities, including anti-obesity, anti-oxidation, anti-osteoporosis, hypoglycemic, anti-fatigue, and anti-cancer. Mei-Gin is the concentrated extract of plum fruit. However, the functional components and physiological effects of the plum fruit are destroied during the long time heating process. Therefore, this research used Mei-Gin formulas which are based on Mei-Gin and added different proportions of plum fruit, black garlic, and Mesona procumbens Hemsl. extracts to prepare seven kinds of Mei-Gin formulas. High-fat/cholesterol diet was used to induce hamsters with hyperlipidemia and the potential on hypolipidemia of these formulas was evaluated. The content is divided into two parts: (i) An animal pretest to screen the most potential sample from different Mei-Gin formulas. (ii) An animal test to evaluate the hypolipidemic effect on different doses of Mei-Gin formula 4. The results of animal pretest showed that Mei-Gin formula 4 could decrease the concentration of serum triglyceride, total cholesterol, and LDL-C. Furthermore, it also reduced the accumulation of hepatic total lipid and promoted the excretion of fecal cholesterol. From these results, Mei-Gin formula 4 was the most effective formula on improving hyperlipidemia. The results of animal test showed that treatment by Mei-Gin formula 4 (100 mg/kg b.w.) could significantly reduce the concentration of serum triglyceride, total cholesterol, and malondialdehyde. Stimultaneously, it also decreased the amount of hepatic total lipid and triglyceride. Besides, it was able to increase the release of fecal total lipid. We explored the hepatic tissue genes of hyperlipidemic hamsters and found that Mei-Gin formula 4 not only promoted the expression of LXR α, ABCG5, ABCA1, and CYP51, but also inhibited the expression of ACC, FAS, DGAT-2, HMG-CoA reductase, SREBP-1a, and SREBP-1c. In addition, it increased the richness and diversity of the gut microbiota in hyperlipidemia hamsters. Also, it increased the number of Lactobacillus acidophilus and Bifidobacterium animalis, and reduced Helicobacter pylori abundance, which could improve cholesterol metabolism and inhibited its synthesis to reach hypolipidemic effect. Based on these results, Mei-Gin formula 4 had the function to improve dyslipidemia in high-fat/cholesterol-diet-induced hamsters. It would be used to develop into health food to regulate serum lipid profiles in the future.

全文摘要………………………………………………………………….i
英文摘要..……..………………………………………………………....ii
目次…...………………………………………………………………....iv
圖次…………………………………………………………………..... vii
表次……………………………………………………………………...ix
縮寫表…………………………………………………………………...xi
壹、前言……………………………………………………………….....1
貳、文獻整理…………………………………………………………….3
一、高血脂概述 (Hyperlipidemia overview)……...………………..4
(一) 國人血脂概況……………………………………………4
(二) 何謂高血脂………………………………………………8
二、脂質代謝 (Lipid metabolism) …………..……………………15
(一) 脂質外源性路徑………………………………..………15
(二) 脂質內源性路徑……..…………………………………16
三、肝臟與脂質代謝 (Liver and lipid metabolism)………….......17
四、脂蛋白與載脂蛋白 (Lipoprotein and apolipoprotein)..……...19
(一) 脂蛋白簡介………………………………………….….19
(二) 載脂蛋白簡介…………………………………….…….22
五、肝臟組織基因 (Hepatic tissue gene)………………………...24
六、胃腸道微生物 (Gastrointestinal microbiome)…………..……27
(一) 消化道簡介……………………………………….…….27
(二) 腸道菌群組成簡介…………….………………….……28
(三) 飲食與菌群組成相關性……..…………………………31
七、梅精複方 (Mei-Gin formula)…………………………………33
(一) 青梅與梅精概述………………………………......……33
(二) 黑蒜概述……………………………………………..…35
(三) 仙草概述……………………………………………..…36
八、研究目的………………………………………………………40
九、研究架構………………………………………………………41
參、材料方法.…………………………………………………………..42
肆、結果…….…………………………………………………………...55
一、以高脂/膽固醇飲食誘導倉鼠高血脂進行不同梅精複方之篩
選……………………………………………………………..55
(一) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之生理參
數影響………………………………………………………..55
(二) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之臟器及
內臟脂肪組織重量變化……………………………………..55
(三) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之血脂及
血糖含量影響……..…………………………………………56
(四) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之血清
HDL-C、LDL-C 和 HDL-C/LDL-C 比例分析…………...56
(五) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之肝臟與
腎臟安全性指數及電解質平衡分析………………………..56
(六) 梅精複方對高脂/膽固醇飲食誘導倉鼠高血脂之肝臟及
糞便脂質含量分析…………………………………………..57
二、不同劑量梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之
改善效應……………………………………………………..58
(一) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之生
理參數影響…..………………………………………………58
(二) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之臟
器及內臟脂肪組織重量變化………...……………………...58
(三) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之血
脂及血糖含量分析…………….………..…………………...59
(四) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之血
清 HDL-C、LDL-C、HDL-C/LDL-C 比例和丙二醛分析.59
(五) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之肝
臟與腎臟安全性指數及電解質平衡分析……………..……60
(六) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之肝
臟及糞便脂質含量分析……………………………………..60
(七) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之肝
臟及腎臟之 HE 染色分析…………………..…..………..61
(八) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之肝
臟基因表現影響……………………………………………..62
(九) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之糞
便微生物群聚組成相似性分析……………………………..62
(十) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之糞
便微生物 α 多樣性分析……………….………...………....63
(十一) 梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之
Heatmap 糞便菌相組成分析………....……………………..64
三、梅精複方 4 之機能性成分分析…………………………….64
伍、討論…………………………………………………………………65
一、以高脂/膽固醇飲食誘導倉鼠高血脂進行不同梅精複方之篩
選……………………………………………………………..65
二、不同劑量梅精複方 4 對高脂/膽固醇飲食誘導倉鼠高血脂之
改善效應……………………………………………………..69
陸、總結論………………………………………………………………79
柒、參考文獻…………………………………………………………..115

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