臺灣博碩士論文加值系統

益生菌為藉由改善腸道內微生物菌相平衡而有益於宿主的活菌，目前已被證實具預防代謝性疾病之功效。本研究探討副乾酪乳酸桿菌副乾酪亞種 NTU 101 (Lactobacillus paracasei subsp. paracasei NTU 101, NTU 101) 對高膽固醇及高油脂飲食動物其脂質代謝及腸道微生物多樣性之影響。第一部份以 NTU 101 及以深層海水培養之 NTU 101 (NTU 101-DSW) 餵食高膽固醇飲食倉鼠探討其調節血脂之功效；第二部分為餵食 NTU 101 及其發酵豆奶水萃取物 (NTU 101-SM) 評估減少體脂肪生成之功效；並利用聚合酶鏈反應結合變性梯度膠體電泳 (polymerase chain reaction- denaturing gradient gel electrophoresis) 分析高膽固醇及高油脂飲食動物之腸道微生物多樣性。結果顯示，餵食NTU 101及 NTU 101-DSW 之倉鼠與高膽固醇飲食組相比，顯著降低血清中總膽固醇 (total choleaterol, TC)、三酸甘油酯 (triglyceride, TG) 之濃度、低密度脂蛋白膽固醇及高密度脂蛋白膽固醇之比例與肝臟中 TC 與 TG 之濃度 (p < 0.05)。在抗氧化指標方面，餵食 NTU 101及 NTU 101-DSW 之高膽固醇飲食倉鼠血清丙二醛濃度顯著降低 (p < 0.05)，且會增加血液中超氧化物歧化酶及過氧化氫酶之活性 (p < 0.05)。餵食 NTU 101 及 NTU 101-SM 大鼠其食物利用率、體重增加量及總脂肪量與高油脂飲食組相比顯著減少 (p < 0.05)。此外，餵食高膽固醇及高油脂飲食皆會影響腸道微生物之菌相，且高膽固醇飲食比高油脂飲食對腸道微生物菌相影響更大；而 NTU 101、NTU 101-DSW 及 NTU 101-SM 皆會造成腸道微生物之多樣性之改變，且餵食 NTU 101-DSW 之倉鼠可顯著增加腸道中乳酸桿菌數量 (p < 0.05)。綜合以上結果，NTU 101、NTU 101-DSW 及 NTU 101-SM 能改變高膽固醇及高油脂飲食動物之腸道菌相，並能調節血脂及減少體脂肪形成，表示腸道微生物之組成與脂質代謝具有高度相關性。

Probiotics are live microorganisms thought to be beneficial to the host organisms by improving its intestinal microbial equilibrium and have been reported to play an important role in the prevention of metabolic disorders. The objective of this study was to determine the effect of Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) on lipid metabolism and diversity of intestinal microorganisms of rats fed with high fat and high cholesterol diet. In the first part, hypercholesterolemic hamsters were orally administrated with NTU 101 and the NTU 101 cultured in deep seawater (NTU 101-DSW) to determine the effect on blood lipids. In the second part, NTU101 and the water extract of fermented soy milk with NTU 101 (NTU 101-SM) were orally administrated to the high fat diet rats to evaluate the inhibitory effects of body fat. Finally, the polymerase chain reaction- denaturing gradient gel electrophoresis was used to investigate the diversity of intestinal microflora in hypercholesterolemic hamsters and hypertriglyceridemic rats. The results indicated that total cholesterol (TC) and Triglyceride (TG) levels, the ratio of low density lipoprotein cholesterol to high density lipoprotein cholesterol of serum, and total liver TC and TG were significant decreased after feeding with NTU 101, NTU 101-DSW, compared with high cholesterol group. In addition, the level of the activities of superoxide dismutase and catalase were significantly increased in the DSW, NTU 101, NTU 101-DSW groups (p < 0.05), as compared to those in the high cholesterol group. The feed efficiency, body weight gain and total fat were significantly reduced by feeding with NTU101 and water extract from soy milk fermented with NTU101, as compared to those in the high fat group (p < 0.05). Furthermore, high cholesterol and high fat diets affected the intestinal microbial microflora, and high cholesterol diet affected the intestinal microflora more than high fat diet. The intestinal microbial diversity were changed by administrating NTU 101, NTU 101-DSW and NTU 101-SM, and the viable cell numbers of Lactobacillus spp. in hamsters’ cecum were significantly increased (p < 0.05). In conclusion, NTU101, NTU 101-DSW and NTU 101-SM changed the gut microflora, regulated the blood lipid, and reduced body fat of rats fed with high cholesterol and high fat diet. Indicates the composition of gut microflora and lipid metabolism are highly correlated.

第一章 緒言 ………………………………………………………………………... 1
第二章 文獻回顧 …………………………………………………………………... 3
2.1 代謝症候群之定義 ……………………..…………………………………... 3
2.2 高血脂症與肥胖 …………………………...……………………………….. 3
2.2.1 高血脂症 …………………………….…………………………………... 5
2.2.2 肥胖 ………………………………………...….………………………… 7
2.2.3 高血脂症及肥胖之相關疾病 …………………………………………… 8
2.3 脂質代謝 .……………………………………...….………………………… 9
2.3.1 脂質之吸收 …..…………………………………...….………………….. 9
2.3.2 膽固醇之合成及運送 ………………………………………...….……… 9
2.4 深層海水之介紹與保健功效 ………………………………………...…… 17
2.4.1 深層海水定義 ..……………………………………...….……………… 17
2.4.2 深層海水的特性 ..……………………………………...….…………… 17
2.4.3. 深層海水之生理功效 ………………………………………...….……. 18
2.4.4 深層海水發酵產物之保健功效 ……………………………………….. 20
2.5益生菌及乳酸菌 ………………….…………………...….………………... 20
2.5.1益生菌之介紹 ……………………….……………...….……………….. 20
2.5.2 乳酸菌 ..……………………………………...….……………………… 20
2.5.3 乳酸菌之分類 ………………………………………...….…………….. 21
2.5.4 乳酸菌之生理功效 ………………………………………...….……….. 21
2.6 副乾酪乳酸桿菌副乾酪亞種 NTU 101 ……..…………………………... 24
2.6.1 副乾酪乳酸桿菌副乾酪亞種 NTU 101 之生理功效 …………..……. 24
2.7 腸道微生物與代謝 ………………………………………...….…………... 26
第三章 研究目的與實驗架構 ………………………………………...….………. 27
第四章 材料與方法 ..……………………………………………………………... 29
4.1 試驗菌株 ..…………………………………………………………………. 29
4.2 化學藥品 …………………………………………………………………... 29
4.3 動物飼料 ..…………………………………………………………………. 30
4.4 儀器設備 ..…………………………………………………………………. 30
4.5 高膽固醇飲食動物試驗模式系統 …………..…………………………..... 31
4.6 高油脂飲食動物試驗模式系統 ..……………………………………….… 39
4.7 腸道微生物之菌相及多樣性分析 ..…………………………………..…... 45
4.8 統計分析 ..………..…………………………………………………….….. 46
第五章 結果與討論 ………………………………………………………...…….. 49
5.1 以深層海水培養 NTU101 對調節體內血脂之動物實驗評估 …………. 49
5.1.1 血漿中總膽固醇、三酸甘油酯、低密度脂蛋白膽固醇及高密度脂蛋白膽固醇之濃度 ..……………………………………………………………….. 49
5.1.2肝臟組織及糞便中總膽固醇、三酸甘油酯之濃度 ……………………. 52
5.1.3 血液中各項氧化指標之分析 ………………………………………….. 52
5.1.3.1 血液中脂質過氧化程度 ……………………………………………. 52
5.1.3.2 血液中抗氧化酵素之活性 ………………………………………..... 54
5.1.4 心臟主動脈脂質堆積程度 …………………………………………….. 55
5.1.5 血清中 AST、ALT 活性之影響 ………………………………………………………. 55
5.1.6 高膽固醇飲食對倉鼠體內腸道微生物及菌相多樣性之影響 …...…... 62
5.2 NTU101及其發酵豆奶水萃取物對減少體脂肪之功效評估 …...……….. 71
5.2.1 體重、攝食量及食物利用率 ……………………………...……………. 71
5.2.2 體脂肪量及總粗脂肪量與百分比 …………………………………….. 71
5.2.3 脂肪組織中脂解酶活性 ……………………………………….............. 72
5.2.4 脂肪組織中 heparin-releasable LPL 活性測定 ………..…………….. 72
5.2.5 安全性評估 ………………………………………...….……………….. 78
5.2.5.1 血脂質濃度 ……………………………..………...….……………... 78
5.2.5.2 肝組織及盲腸中脂質之濃度…………..…………………………..... 78
5.2.5.3 主動脈脂質斑塊 ……………………..………………...….………... 78
5.2.5.4 禁食血糖及胰島素濃度測定 ……………..………………………... 79
5.2.5.5血清肝指數、腎指數 及電解質 …………………………………… 79
5.2.6高油脂飲食對大鼠體內腸道微生物及菌相多樣性之影響 ………….... 80
5.3討論 ………………………………………...….……………………………. 95
5.3.1 乳酸菌調節血脂及肥胖 ……………………………………...….…….. 95
5.3.2 深層海水調節血脂與肥胖 ……………..………………………...….… 99
5.3.3 乳酸菌對腸道菌相之影響 ………………………………………...…. 100
第六章 總結 ………………………………………...….…..……………………. 103
第七章 參考文獻 ………………………………………………………………... 104

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