臺灣博碩士論文加值系統

樟芝（Antrodia cinnamomea, AC）是台灣特有的藥用真菌。本實驗的研究目的是探討樟芝對於倉鼠肝臟蛋白質體的影響。餵飼八週齡的雄性敘利亞倉鼠一般飼料（n = 10）或高脂飼料（21%脂肪及0.15%膽固醇）（n = 40）四週後，再餵飼高脂組的倉鼠樟芝菌絲體粉末12週（一倍、兩倍及五倍劑量樟芝組分別給予為111, 222, 555 mg/kg BW/day）。實驗期結束後，採集血液和肝臟進行分析。將肝臟蛋白質以電泳分離，經胰蛋白酶（trypsin）水解後透過nano-LC/MS/MS分離，將質譜分析結果經由TurboSequest演算法鑑定之胜肽序列與蛋白質資料庫（Universal Protein Resource Knowledgebase, UniProt）的倉鼠資料庫比對。結果顯示，餵飼樟芝能降低血清三酸甘油酯及總膽固醇濃度、增加糞便膽酸排除（p < 0.05）。從蛋白質體學分析中，共比對出1117個肝臟蛋白質，其中有78個的表現受到高脂飼料的顯著影響（p < 0.05）、289個的表現受到樟芝的顯著影響（p < 0.05）。樟芝降低發炎標記物膜聯蛋白（annexin A3, ANXA3)、促發炎蛋白環氧化酶（cyclooxygenase-2, COX-2）和載脂蛋白（apolipotein E, apoE）的表現。此外，樟芝增加參與糖解的甘油-3-磷酸脫氫酶（glycerol-3-phosphate dehydrogenase, GPDH）和參與β-oxidation的hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase的α-subunit (HADHA) 的表現。

Antrodia cinnamomea (AC) is a treasured endemic Taiwanese medicinal mushroom. The purpose of this study was to evaluate the effect of Antrodia cinnamomea on hepatic proteomic of hamster. Eight-week old male Syrian hamsters were fed control diet (n=10) or high fat diet (21% fat and 0.15% cholesterol) (n=40) for four weeks, followed by administration of AC mycelia powder (111, 222, and 555 mg/kg/day for 1 x AC, 2 x AC, 5 x AC groups, respectively) with high-fat diet for another 12 weeks. At the end of study, blood and livers were collected for analysis. Liver proteins were fractionated by electrophoresis, digested by trypsin, and then separated by label-free nano-LC/MS/MS. The TurboSequest algorithm was used to identify the peptide sequences against the hamster database in Universal Proteins Resource Knowledgebase (UniProt). Administraton of AC significantly (p<0.05) decreased serum triglyceride and total cholesterol concentration but increased excretion of fecal bile acids in high-fat groups. Proteomic analysis indicated that 1117 hepatic proteins were identified and 78 of them were expressed differently in high-fat group (p<0.05). Among the 1117 proteins, 289 hepatic proteins were significantly (p<0.05) affected by AC. Supplementation of AC down-regulated inflammatory markers annexin A3 (ANXA3), pro-inflammatory protein cyclooxygenase-2 (COX-2) ,and apolipoprotein E (apoE). Moreover, glycerol-3-phosphate dehydrogenase (GPDH) involved in glycolysis and the α-subunit of hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (HADHA) which involves in β-oxidation were up-regulated by AC.

目錄
致謝 I
目錄 II
圖目錄 VII
表目錄 VIII
摘要 IX
Abstract X
前言 1
背景 2
壹、樟芝 2
一、樟芝簡介 2
二、樟芝功效 3
(一)抗發炎 3
(二)抗癌症 5
(三)保護肝臟 6
貳、蛋白質體學 7
一、簡介 7
二、表現蛋白質體學 8
三、操作技術 8
(一)蛋白質分離 8
(二)蛋白質鑑定質譜儀 8
1.質譜儀 8
2.串聯式質譜儀（tandem mass spectrometry, MS/MS） 9
(三)資料庫搜尋比對 9
(四)Ingenuity Pathways Analysis (IPA) 10
材料與方法 11
一、樟芝來源 11
二、實驗動物飼養 11
三、血液生化值分析 13
(一)血清樣本製備 13
(二)血清三酸甘油酯分析 13
(三)血清總膽固醇分析 13
(四)血清高密度脂蛋白膽固醇分析 14
(五)血清非高密度脂蛋白膽固醇分析 14
(六)血清天門冬胺酸轉胺酶分析 14
(七)血清丙胺酸轉胺酶分析 15
四、肝臟脂質分析 15
(一)肝臟脂質萃取 15
1.分析肝臟三酸甘油酯及膽固醇含量 16
2.分析肝臟三酸甘油酯含量 16
3.分析肝臟膽固醇含量 16
五、糞便分析 16
(一)糞便脂質萃取 16
(二)分析糞便三酸甘油酯及膽固醇含量 17
1.分析糞便三酸甘油酯含量 17
2.分析糞便膽固醇含量 17
(三)糞便膽酸分析 18
六、質譜分析前置作業 18
(一)肝臟均質與細胞質分離 18
(二)肝臟細胞質蛋白質濃度定量 18
(三)SDS-PAGE 19
(四)蛋白質膠內酵素水解法 21
七、Nano-LC/MS/MS質譜分析 21
八、資料庫檢索 22
九、Ingenuity Pathways Analysis (IPA) 22
十、西方點墨法（Western blotting, WB） 23
(一)SDS-PAGE 23
(二)Transfer and Blocking 23
(三)Probing 25
(四)Chemiluminecsent Detection 25
(五)Stripping and Reprobing 25
十一、統計與分析 28
結果 29
一、樟芝對於倉鼠體重、飼料攝取率及臟器重的影響 29
二、樟芝對於倉鼠血液生化值的影響 33
(一)血清三酸甘油酯濃度、總膽固醇、高密度與低密度脂蛋白膽固醇 33
1.血清三酸甘油酯濃度（triglyceride, TG） 33
2.血清總膽固醇濃度（total cholesterol, TC） 35
3.血清高密度與低密度脂蛋白膽固醇 37
(二)血清天門冬胺酸轉胺酶與丙胺酸轉胺酶活性 37
1.血清天門冬胺酸轉胺酶活性（AST） 37
2.血清丙胺酸轉胺酶活性（ALT） 42
三、樟芝對於倉鼠肝臟脂質的影響 42
(一)肝臟三酸甘油酯含量（triglyceride, TG） 42
(二)肝臟膽固醇含量（total cholesterol, TC） 42
四、樟芝對於倉鼠糞便脂質的影響 46
(一)糞便三酸甘油酯含量 46
(二)糞便膽固醇含量 46
(三)糞便膽酸含量 46
五、對照組與高脂組倉鼠肝臟蛋白質表現的比較 46
(一)肝臟表現差異蛋白質 46
(二)以IPA歸納對照組與高脂組倉鼠肝臟表現差異蛋白質之生物功能與參與的典型路徑 46
1.肝臟表現差異蛋白質之生物功能性 74
2.肝臟表現差異蛋白質之毒性功能 74
六、高脂組與樟芝組倉鼠肝臟蛋白質表現的比較 74
(一)肝臟表現差異蛋白質 74
(二)樟芝組與對照組和高脂組相比之差異蛋白質 74
(三)西方點墨法（Western blotting, WB） 113
1.aconitase 2 (ACO2) 113
2.annexin A3 (ANXA3) 113
3.apolipoprotein (apoE) 113
4.cyclooxygenase-2 (COX-2) 113
5.cytochrome P450 2E1 (CYP2E1) 113
6.glycerol-3-phosphate dehydrogenase (GPDH) 113
7.glutathione S-transferase alpha 4 (GSTA4) 113
8. 3-hydroxyacyl-CoA dehydrogenase type-2 (HADHA) 113
9.monoglyceride lipase (MGLL) 122
10.protein phosphatase 2, regulatory subunit A (PPP2R1A) 122
討論 126
一、樟芝對於倉鼠飼料攝取、體重及臟器重的探討 126
二、樟芝對於倉鼠體內生化指標的探討 126
三、樟芝對於倉鼠排除體外的糞便及膽酸影響 127
四、樟芝對於倉鼠肝臟蛋白質體的探討 129
(一)aconitase 2 (ACO2) 129
(二)annexin A3 (ANXA3) 131
(三)apolipoprotein E (apoE) 131
(四)cyclooxygenase-2 (COX-2) 132
(五)cytochrome P450 2E1 (CYP2E1) 134
(六)glycerol-3-phosphate dehydrogenase (GPDH) 136
(七)glutathione S-transferase alpha 4 (GSTA4) 138
(八)3-hydroxyacyl-CoA dehydrogenase type-2 (HADHA) 138
(九)monoglyceride lipase (MGLL) 139
(十)protein phosphatase 2, regulatory subunit A (PPP2R1A) 141
參考文獻 142

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