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研究生:簡慈美
研究生(外文):Tzu-Mei Chien
論文名稱:三葉五加莖部萃取物之抗炎活性暨高血糖、高血脂及高血壓之台灣全民健保中醫用藥分析研究
論文名稱(外文):Study on the Anti-inflammatory Activity of the Extract of Acanthopanax trifoliatus Stem and Analysis of Prescriptions of Chinese Herbal Medicine for Diabetes Mellitus, Hyperlipidemia and Hypertension under the National Health Insurance in Taiwan
指導教授:張永勳張永勳引用關係
指導教授(外文):Yuan-Shiun Chang
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:中國藥學暨中藥資源學系博士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:184
中文關鍵詞:三葉五加脂多醣體急性肺損傷台灣全民健保中藥中醫
外文關鍵詞:Acanthopanax trifoliatusLipopolysaccharide( LPS )Acute lung injury( ALI )National Health InsuranceChinese herbTraditional Chinese Medicine
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三葉五加莖部萃取物之抗炎活性
三葉五加是台灣普遍用來治療瘀青、神經痛、陽痿和痛風的植物。本研究探討三葉五加在體外及體內抑制 LPS 誘導之發炎反應。在體外以 LPS 刺激小鼠巨噬細胞株 RAW 264.7 產生發炎反應,在體內以 LPS 誘導小鼠的肺損傷,並檢測三葉五加乙酸乙酯( EAAT )層萃取物的抗炎作用。採用enzyme-linked immunosorbent assay ( ELISA ) and Western blot 之方法檢測 EAAT 對 LPS 誘導的Raw264.7小鼠巨噬細胞和小鼠模型中的炎症介質的產生效果。 EAAT可降低體外和體內以 LPS 誘導產生發炎之一氧化氮(NO),腫瘤壞死因子-α(TNF-α),interleukin 1β(IL-1β)及 IL-6 。預先投與 EAAT ,能顯著降低 LPS 誘導的小鼠肺組織改變。此外, EAAT顯著降低 BALF 中的總細胞和蛋白質數量。EAAT 阻斷誘導一氧化氮合A酶(iNOS)的蛋白表現,環氧合酶-2(COX-2),在 LPS 刺激的RAW 264.7細胞和 LPS 誘導的肺損傷的磷酸化IκB-α蛋白和阻斷 MAPKs的路徑。本研究顯示三葉五加可抑制 LPS誘導之發炎反應,具有發展為抗發炎天然藥物之潛力。
高血糖、高血脂及高血壓之台灣全民健保中醫用藥分析研究
我國自民國84年3月起辦理全民健康保險,全體國民一律強制投保,至100年底納保率已達99.8﹪以上,醫療院所健保特約亦達93.5 %以上,中醫診所健保特約亦達91.6%以上,健保資料庫涵蓋範圍幾達所有國民,具有相當重要的研究價值與代表性。近年來,中醫藥療效受到全球之肯定與重視,本研究係藉由全體健保特約醫療院所申報之100年1月至12月份之中醫門診處方及治療明細檔、中醫門診處方醫令明細檔等資料統計分析,以建立台灣地區中醫門診之用藥資料,並進行高血糖、高血脂、高血壓之中醫用藥情形分析研究。
本研究結果主要發現如下:
一、100年健保中醫門診用藥量為複方7,991公噸,單方2,682公噸,合計10,673公噸,複方用量遠高於單方,其比例約為75:25。
二、100年健保中藥複方用量最多之前10名為依次為加味逍遙散、葛根湯、疏經活血湯、半夏瀉心湯、辛夷清肺湯、小青龍湯、小柴胡湯、芍藥甘草湯、麻杏甘石湯、平胃散;中藥單方用量最多之前10名為依次為大黃、延胡索、丹參、黃芩、桔梗、貝母、半夏、葛根、附子、黃耆。
三、100年僅因糖尿病而使用健保中醫門診中藥治療之人數為27,168人,占健保門急診糖尿病總患者人數之1.75%。在年齡方面,以50至59歲年齡層31.2%為最多。
四、100年糖尿病健保中藥複方使用次數最多之前10名依次為六味地黃丸、玉泉丸、白虎加人參湯、濟生腎氣丸、知柏地黃丸、八味地黃丸、杞菊地黃丸、白虎湯、甘露飲、生脈飲;糖尿病健保中藥單方使用次數最多之前10名依次為栝樓根、丹參、黃耆、山藥、玄參、葛根、大黃、麥門冬、石斛、蒼朮。
五、100年僅因高血脂而使用健保中醫門診中藥治療之人數為23,714人,占健保門急診高血脂總患者人數之1.19%。在年齡方面,以50至59歲年齡層31.9%為最多。
六、100年高血脂健保中藥複方使用次數最多之前10名依次為血府逐瘀湯、防風通聖散、大柴胡湯、加味逍遙散、溫膽湯、茵陳五苓散、小柴胡湯、龍膽瀉肝湯、六味地黃丸、補陽還五湯;高血脂健保中藥單方使用次數最多之前10名依次為紅麴、山楂、丹參、何首烏、決明子、澤瀉、大黃、荷葉、茵陳、黃耆。
七、100年僅因高血壓而使用健保中醫門診中藥治療之人數為36,792人,占健保門急診高血壓總患者人數之1.35%。在年齡方面,以50至59歲年齡層28.5%為最多。
八、100年高血壓健保中藥複方使用次數最多之前10名依次為天麻鈎藤飲、鈎藤散、血府逐瘀湯、知柏地黃丸、加味逍遙散、龍膽瀉肝湯、六味地黃丸、補陽還五湯、半夏天麻白朮湯、柴胡加龍骨牡蠣湯;高血壓健保中藥單方使用次數最多之前10名依次為丹參、鈎藤、葛根、川牛膝、夏枯草、大黃、決明子、天麻、山楂、黃芩。

Acanthopanax trifoliatus is a well-known herb that is used for the treatment of bruising, neuralgia, impotence, and gout in Taiwan. This study investigated the in vitro and in vivo anti-inflammatory effect of A. trifoliatus. An anti-inflammatory effect of EAAT was detected using lipopolysaccharide (LPS) stimulation of the mouse macrophage cell line RAW264.7 in vitro and LPS-induced lung injury in vivo. The effects of EAAT on LPS-induced production of inflammatory mediators in Raw264.7 murine macrophages and the mouse model were measured using enzyme-linked immunosorbent assay and Western blot. EAAT attenuated the production of LPS-induced nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin?{1β (IL-1β)and IL-6 in vitro and in vivo. Pretreatment with EAAT markedly reduced LPS-induced histological alterations in lung tissues. Furthermore, EAAT significantly reduced the number of total cells and protein concentration levels in the BALF. Western blotting revealed that EAAT blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of IκB-α protein and MAPKs in LPS-stimulated RAW 264.7 cells, and LPS-induced lung injury was also blocked. This study suggests that A. trifoliatus may be a potential therapeutic candidate for the treatment of inflammatory diseases.

The National Health Insurance in Taiwan was initiated in March 1995. All nationals of the Republic of China are obligated by law to join the NHI program. At the end of 2011, the coverage rate went up to more than 99.8%. The contract rate of hospitals and clinics was over 93.5%. The National Health Insurance Research database is massive and analysis results could provide an important reference of medical care models and medical cost.
In recent years, Chinese medicine has been getting more and more popular in the world. This study collected and analyzed the National Health Insurance Research database in Ambulatory care expenditures by visits of Chinese medicine and Details of ambulatory care orders of Chinese medicine from January to December in 2011.
There are some main findings:
1.A total of 10,673,000 kg of Chinese crude drug preparations was used for care at Chinese medicine in 2011, including Chinese herbal formulae 7,991,000 kg and single herbs 2,682,000 kg, compound- single weight ratio is 75:25.
2.In 2011, the top 10 of compound formula in weight order of using for care at Chinese medicine were jia wei xiao yao san, ge gen tang , shu jing huo xie tang , ban xia xie xin tang , xin yi qing fei tang , xiao qing long tang , xiao chai hu tang , shao yao gan cao tang , ma xing gan shi tang , ping wei san san . On the other hand, the top 10 of single herbs by weight order of using for care at Chinese medicine were Rhei Radix et Rhizoma, Corydalis Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma , Scutellariae Radix , Platycodi Radix, Fritillariae Thunbergii Bulbus, Pinelliae Rhizoma, Puerariae Radix , Aconiti lateralis Radix , Astragali Radix.
3.In 2011, the compound formula in person-time order of using for care Diabetes Mellitus outpatients at Chinese tranditional medicines were liu wei di huang wan, yu quan wan , bai hu jia ren shen tang, ji sheng shen qi wan, zhi bo di huang wan, ba wei di huang wan, qi ju di huang wan, bai hu tang, gan lu yin, sheng mai yin. Moreover the top 10 of single herbs by person-time order of using for care Diabetes Mellitus outpatients at Chinese tranditional medicine were Trichosanthis Radix, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Dioscoreae Rhizoma , Scrophulariae Radix, Puerariae Radix , Rhei Radix et Rhizoma, Ophiopogonis Radix, Dendrobii Caulis, Atractylodis Rhizoma.
4.In 2011, the compound formula in person-time order of using for care hyperlipidemia outpatients at Chinese tranditional medicines were xie fu zhu yu tang, fang feng tong sheng san, da chai hu tang, jia wei xiao yao san, wen dan tang, yin chen wu ling san, xiao chai hu tang, long dan xie gan tang, liu wei di huang wan, bu yang hai wu tang. Moreover the top 10 of single herbs by person-time order of using for care hyperlipidemia outpatients at Chinese tranditional medicine were Monascus purpureus Went, Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma, Polygoni Multiflori Radix, Cassiae Semen, Alismatis Rhizoma, Rhei Radix et Rhizoma , Lotus Leaf , Artemisiae Scopariae Herba, Astragali Radix.
5. In 2011, the compound formula in person-time order of using for care hypertension outpatients at Chinese tranditional medicines were tian ma gou teng yin, gou teng san, xie fu zhu yu tang, zhi bo di huang wan, jia wei xiao yao san, long dan xie gan tang, liu wei di huang wan, bu yang hai wu tang, ban xia tian ma bai zhu tang, chai hu jia long gu mu li tang. Moreover the top 10 of single herbs by person-time order of using for care hypertension outpatients at Chinese tranditional medicine were Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Puerariae Radix, Cyathulae Radix, Prunellae Spica, Rhei Radix et Rhizoma, Cassiae Semen, Gastrodiae Rhizoma, Crataegi Fructus, Scutellariae Radix.

謝 辭 I
縮寫表 VII
圖目錄 IX
表目錄 X
中文摘要 XII
英文摘要 XVI
壹、三葉五加莖部萃取物之抗炎活性 1
第一章 緒論 1
第二章 總論 4
第一節 三葉五加之藥用植物學考察 4
第二節 發炎反應 6
第三節 急性肺損傷 8
第四節 一氧化氮與發炎性疾病的關係 12
第三章 研究方法 14
第一節 實驗材料 14
第二節 HPLC定量分析 16
第三節 細胞培養 19
第四節 急性肺損傷動物模式 26
第五節 統計分析 32
第四章 結果 33
第一節 三葉五加莖部HPLC定性定量分析 33
第二節 三葉五加萃取物和分層對於RAW264.7之細胞毒性及存
活率之影響 36
第三節 三葉五加萃取物和分層對RAW264.7細胞產生一氧化氮
之影響 37
第四節 三葉五加乙酸乙酯層在RAW264.7細胞中影響LPS所誘
發之iNOS 及 COX-2 蛋白質表現量 39
第五節 三葉五加乙酸乙酯層藉由 NF-kB 路徑影響發炎反應 40
第六節 在RAW264.7細胞中三葉五加乙酸乙酯層影響MAPK 蛋
白質表現量 41
第七節 三葉五加乙酸乙酯層對RAW264.7細胞之細胞激素影響 44
第八節 誘發急性肺損傷動物模型 47
第九節 支氣管肺泡沖洗液之蛋白質濃度測定和細胞學測定 49
第十節 支氣管肺泡沖洗液之 NO 和細胞激素含量測定 52
第十一節 西方墨點法 55
第五章 討論 57
第六章 結論 62
第七章 參考文獻 64
貳、高血糖、高血脂及高血壓之台灣全民健保中醫用藥分析研究 73
第一章 緒論 73
第一節 研究背景 73
第二節 研究動機 77
第三節 研究目的 77
第四節 研究範圍 78
第二章 總論 79
第一節 十大死因 79
第二節 醫療機構家數 82
第三節 醫事人力 85
第四節 藥商家數 93
第五節 全民健保醫療費用申報概況 94
第三章 研究方法與步驟 100
第一節 資料來源 100
第二節 研究方法 100
第三節 研究步驟 100
第四節 門診處方及治療明細檔格式 102
第五節 門診處方醫令明細檔格式 105
第六節 健保資料檔串檔說明 106
第四章 研究結果 107
第一節 健保複方中藥用量排行 107
第二節 健保單方中藥用量排行 121
第三節 高血糖全民健保中醫用藥分析 137
第四節 高血脂全民健保中醫用藥分析 150
第五節 高血壓全民健保中醫用藥分析 162
第五章 討論 175
第六章 結論 178
第七章 參考文獻 180

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高血糖、高血脂及高血壓之台灣全民健保中醫用藥分析研究
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3.衛生福利部統計處首頁/衛生福利統計專區/醫療機構現況及醫院醫療服務量統計/年報/100年度醫療服務量/四、100年醫療院所概況 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=2633 )
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8.衛生福利部統計處首頁/衛生福利統計專區/死因統計/102年度死因統計/統計表/102年度死因統計年報(http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5150)
9.衛生福利部統計處首頁/衛生福利統計專區/死因統計/102年度死因統計/統計表/102年死因統計結果分析 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5150)
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11.衛生福利部統計處首頁/衛生福利統計專區/醫療機構現況及醫院醫療服務量統計/年報/102年度醫療服務量/一、歷年醫療院所概況/表2歷年醫療院所家數-按型態別分(http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5048)
12.衛生福利部統計處首頁/衛生福利統計專區/醫療機構現況及醫院醫療服務量統計/年報/102年度醫療服務量/一、歷年醫療院所概況/表5歷年醫療院所執業醫事人員數 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5048)
13.衛生福利部統計處首頁/衛生福利統計專區/醫療機構現況及醫院醫療服務量統計/年報/102年度醫療服務量/一、歷年醫療院所概況/表6歷年醫療院所每萬人口執業醫事人員數 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5048)
14.衛生福利部統計處首頁/衛生福利統計專區/醫療機構現況及醫院醫療服務量統計/年報/102年度醫療服務量/四、102年醫療院所概況/表29醫療院所每萬人口執業醫事人員數-按縣市別分 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5051)
15.衛生福利部統計處首頁/衛生福利統計專區/公務統計報表/衛生類公務統計/食品及藥物管理統計/藥政管理/藥商別 (http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=5475)
16.衛生福利部中央健康保險署編印:中華民國102年全民健康保險統計,103年10月,p.156-157
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18.衛生福利部統計處首頁/衛生福利資料統計應用中心/申請資料相關文件/表單下載/資料庫使用手冊/全民健保處方及治療明細檔_門急診 (http://www.mohw.gov.tw/CHT/DOS/DM1.aspx?f_list_no=812&fod_list_no=4815 )
19.衛生福利部統計處首頁/衛生福利資料統計應用中心/申請資料相關文 件/表單下載/資料庫使用手冊/全民健保處方及治療醫令明細檔─西醫、中醫及牙醫門診(http://www.mohw.gov.tw/CHT/DOS/DM1.aspx?f_list_no=812&fod_list_no=4815 )
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24. Weidong Xie, Yunan Zhao, Lijun Du, Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia. Original Research Article. Journal of Ethnopharmacology, Volume 140, Issue 2, 27 March 2012, Pages 345-367
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