跳到主要內容

臺灣博碩士論文加值系統

(54.224.117.125) 您好!臺灣時間:2022/01/28 19:47
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:許勝發
研究生(外文):Sheng-Fa Hsu
論文名稱:六味地黃丸降血糖作用之研究
論文名稱(外文):Antihyperglycemic Action of Die-Huang-Wan
指導教授:鄭瑞棠鄭瑞棠引用關係
指導教授(外文):Juei-Tang Cheng
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
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:2002
畢業學年度:90
語文別:中文
論文頁數:92
中文關鍵詞:六味地黃丸
外文關鍵詞:die-huang-wan
相關次數:
  • 被引用被引用:8
  • 點閱點閱:1434
  • 評分評分:
  • 下載下載:213
  • 收藏至我的研究室書目清單書目收藏:3
近年,隨著人們生活品質的提昇及物質富裕,使得糖尿病患者有日益增加的趨勢。為了協助糖尿病的改善,希望由古代藥方來研發出有效的治療用藥。六味地黃丸乃我國古代一種藥方。在體內 (in vivo) 實驗方面,口服投予六味地黃丸到普通老鼠後,可產生濃度遞增性(dose-dependent)的降血糖作用。但是,給予類似人類糖尿病第一型胰島素依賴型糖尿病(insulin-dependent diabetes mellitus,IDDM)的老鼠,則看不到作用;表示此降血糖作用可能與胰島素有關。以腹腔注射Atropine或Scopolamine再經口投予六味地黃丸,發現它們皆可抑制六味地黃丸降血糖的作用。若給予Physostigmine再經口投予六味地黃丸,則可增強六味地黃丸降血糖的作用;表示六味地黃丸的降血糖作用與副交感神經有關。另外,給予Vesamicol或Hemichoninium-3,將神經末端Acetylcholine濃度減少,則六味地黃丸降血糖作用也跟著減少;表示六味地黃丸降血糖作用與神經末端Acetylcholine釋放有關。若給予M3受體阻斷劑4-DAMP mustard,發現它會以濃度遞增方式阻斷六味地黃丸降血糖的作用;表示六味地黃丸的降血糖作用與M3受體有關。可是,給予Hexamethonium或Pentolinium再投予六味地黃丸,發現降血糖效果不變,故六味地黃丸的降血糖作用與自主神經節的活化無關。由此可知,六味地黃丸降血糖的作用應是藉由副交感神經尾端刺激Acetylcholine釋放,使之作用在胰臟的M3受體,導致胰島素分泌來產生降血糖作用。另一方面,若將六味地黃丸給予類似人類糖尿病第二型非胰島素依賴型糖尿病(non-insulin-dependent diabetes mellitus,NIDDM)的老鼠,同樣可產生濃度遞增性(dose-dependent)的降血糖作用。一般認為,第二型糖尿病病人主要是因為產生胰島素抗性,使得糖分利用降低,而來導致糖尿病發生。因此,探討了六味地黃丸對胰島素抗性的影響。結果發現,六味地黃丸可增加胰島素敏感性來延緩胰島素抗性的發生。六味地黃丸乃由六種藥材所組成,可能以互相扶佐的方式產生作用。所以,在正常大白鼠、第二型糖尿病老鼠及胰島素依賴型糖尿病大白鼠個別給予六味地黃丸的單一種藥材,結果發現山茱萸在胰島素依賴型糖尿病大白鼠降血糖作用會消失。而且,在缺少山茱萸的六味地黃丸,既使在最高降血糖劑量26 mg/kg下,降血糖作用也幾乎消失。另一方面,山茱萸具有刺激胰島素釋放及藉由副交感神經和M3受體產生降血糖作用,而且其刺激胰島素釋放及降血糖作用和六味地黃丸差不多。因此,如果以刺激胰島素釋放作用來看的話,六味地黃丸應以山茱萸為主。
Die-Huang-Wan is prepared by a mixture of 6 herbs. In Chinese traditional medicine, Die-Huang-Wan is one of the prescriptions for handling of diabetic disorders and this herbal mixture has also been used for a long time in Japan and other Asian area. In an attempt to develop agents without side effect for good handling of diabetes mellitus, Die-Huang-Wan was investigated in the present study. Oral of Die-Huang-Wan produced a dose-dependent hypoglycemic action in Wistar rats. Atropine or scopolamine at an effective dose significantly attenuated the Die-Huang-Wan-induced glucose lowing action in Wistar rats. However, physostigmine increased the Die-Huang-Wan-induced glucose lowing action, indicating that Die-Huang-Wan lowered plasma glucose in rats by activation of the parasympathetic nervous system. The plasma glucose lowering effect of Die-Huang-Wan in Wistar rats was abolished by pretreatment vesamicol or hemichoninium-3, indicating that Die-Huang-Wan lowered plasma glucose in rats by releasing acetylcholine of peripheral parasympathetic nervous system. The plasma glucose lowering effect of Die-Huang-Wan in Wistar rats was also abolished by pretreatment 4-DAPM, indicating that Die-Huang-Wan lowered plasma glucose effect by activation of the M3 receptor. Furthermore, oral of Die-Huang-Wan at the effective dose increased the plasma insulin concentration in Wistar rats and antagonist of M3 receptor abolished this action. But the plasma glucose lowering action of Die-Huang-Wan was not abolished by pretreatment with nicotinic receptor antagonist, either hexamethonium or pentolinum, indicating that Die-Huang-Wan lowered plasma glucose in rats was not by activation of the nicotinic receptor. The obtained results suggest that acetylcholine released from the peripheral parasympathetic nerve seems responsible for the lowering of plasma glucose in Wistar rats by Die-Huang-Wan through an activation of islets M3 receptor. Activation of M3 receptor in the islets by the released acetylcholine can increase the insulin concentration to lower plasma glucose in Wistar rats. Effect on insulin sensitivity of Die-Huang-Wan was also investigated. Administration of Die-Huang-Wan delayed the formation of insulin resistance in rats that were induced by the daily repeated injection of human long-acting insulin and identified using the loss of tolbutamide –induced hypoglycemia. In STZ-induced diabetic rats, daily received oral administrations of Die-Huang-Wan (26 mg/kg, t.i.d.) made an increase of response to exogenous insulin at 7 days later. Increase of insulin sensitivity by Die-Huang-Wan can be considered for the delay of insulin resistance. The present study found that oral administration of Die-Huang-Wan could increase insulin sensitivity and delay the development of insulin resistance in rats. Thus, Die-Huang-Wan may be used as an adjuvant for handling of the diabetic patients with insulin resistance in clinic. Die-Huang-Wan is prepared by a mixture of 6 herbs. The major herb of Die-Huang-Wan, for lowering of plasma glucose was investigated. Oral administration of each the 6 herbs into Wistar or Zucker rats and STZ-induced diabetic rats, plasma glucose lowering action of Corni Fructus disappeared in STZ-induced diabetic rats. The plasma glucose lowering effect of Die-Huang-Wan in Wistar rats was abolished in the absence of Corni Fructus, even at an the maximal dose (26 mg/kg). Also like Die-Huang-Wan, Corni Fructus decreased plasma glucose by activation of the M3 receptor, indicating that Corni Fructus is the major herb for plasma glucose lowering effect of Die-Huang-Wan. In conclusion, the present study investigated the machanism(s) of Die-Huang-Wan for decrease of plasma glucose in rats. The main herb in Die-Huang-Wan is determined as Corni Fructus.
中文摘要3
英文摘要6
縮寫表10
第一章 緒論
第一節 前言13
第二節 研究目的18
第三節 六味地黃丸的特性19
第二章 實驗材料與方法
第一節 實驗動物21
第二節 實驗材料22
第三節 實驗方法25
第三章 實驗結果30
第四章 討論51
第五章 結論56
參考文獻59
附圖表64
自述92
Battezzati, A., Benedini, S., Fattorini, A., Sereni, L.P. and Luzi, L. (2000) Effect of hypoglycemia on amino acid and protein metabolism in healthy humans. Diabetes 49:1543-1551
Boschero, A.C., Szpak-Glasman, M., Cameiro, E.M., Bordin, S., Paul, I. Rojas, E. and Atwater, I. (1995) Oxotremorine potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. Am..J. Physiol. 268:E336-342
Brunetti, A., Goldfine, I.D. (1995) Insulin receptor gene expression and insulin resistance. J. Endocrinol. Invest. 18:398-405
Chang, S.L., Lin, J.G., Chi, T.C., Liu, I.M. and Cheng, J.T. (1999) An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats. Diabetologia 42: 250-255
Cheng, J.T., Liu, I.M., Chi, T.C., Su, H.C. and Chang, C.G. (2000) Stimulation of insulin release in rats by Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine. J.Pharm. Pharmacol. 53:273-276
Chi, T.C., Liu, I.M. and Cheng, J.T. (1998) A simple and rapid model of insulin-resistance in Wistar rats. Chin. Pharm. J. 50:113-121
Donahue, R.P. and Orchard, T.J. (1992) Diabetes mellitus and macrovascular complications. An epidemiological perspective. Diabetes Care 15: 1141-1155
Eizirik, D.L., Sandler, S. and Palmer, J.P. (1993) Repair of pancreatic beta-cells. A relevant phenomenon in early IDDM? Diabetes 42: 1383-1391
Ejiri, K., Taniguchi, H., Ishihara, K., Hara, Y. and Baba, S. (1990) Possible involvement of cholinergic nicotinic receptor in insulin release from isolated rat islets. Diabetes Research & Clinical Practice-Supplement 8:193-199
Filz, H.P. (2000) Insulin sensitizer. A new therapy option for type 2 diabetic patients. MMW Fortschritte der Medizin. 142: 31-33
Garvey, W.T., Olefsky, J.M., Griffin, J., Hamman, R.F and Kolterman, O.G. (1985) The effect of insulin treatment on insulin secretion and insulin action in type 2 diabetis mellitus. Diabetes 34: 222-234
Ginsberg, H.N. (1977) Investigation of insulin sensitivity in treated subjects with ketosis-prone diabetes mellitus. Diabetes 26: 278-283
Goldstein, D.A. and Massry, S.G. (1978) Diabetic nephropathy: clinical course and effect of hemodialysis. Nephron 20:286-296
Gylys, K.H., Mellin, C., Amstutz, R. and Jenden, D.(1992) Characterization of the irreversible inhibition of high-affinity choline transport produced by hemicholinium mustaed. J. Neurochem. 59:1302-1308
Harris, M.I., Hadden, W.C., Knowler, W.C. and Bennett, P.H. (1987). Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in the U.S. population aged 20-74 yr. Diabetes, 36: 523-534
Iismaa, T.P., Kerr, E.A., Wilson, J.R., Carpenter, L., Sims, N. and Biden, T.J. (2000) Quantitative and functional characterization of muscarinic receptor subtypes in insulin-secreting cell lines and rat pancreatic islets. Diabetes, 49: 392-398
Iwase, M., Yamaguchi, M., Yoshinari, M., Okamura, C., Hirahashi, T., Tsuji, H. and Fujishima, M. (1999) A Japanese case of liver dysfunction after 19 months of troglitazone treatment. Diabetes Care. 22: 1382-1384
King, H. (1993) Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care 16: 157-177
Lee, H.C., Curry, D.L. and Stern, J.S. (1989) Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve. Am..J. Physiol. 256:E439-444
Liu, I.M., Niu, C.S., Chi, T.C., Kuo, D.H. and Cheng, J.T. (1999b) Investigations of the mechanism of the reduction of plasma glucose by cold-stress in streptozotocin-induced diabetic rats. Neurosci. 92:1137-1142
Marien, M.R., Richard, J.W., Allaire, C. and Altar, C.A. (1991) Suppression of in vivo neostriatal acetylcholine release by vesamicol receptors in brain. J. Neurochem. 57:1878-1883
Murphy, E.J., Davern, T.J., Shakil, A.O., Shick, L., Masharani, U., Chow, H., Freise, C., Lee, W.M. and Bass, N.M. (2000) Troglitazone-induced fulminant hepatic failure. Acute Liver Failure Study Group. Digestive Diseases & Sciences. 45: 549-553
Okamoto, S., Kimura, K., Kitamura, T., Canas, X., Yoshida, T. and Saito, M. (2000) Proinsulin C peptide obviates sympathetically mediated suppression of splenic lymphocyte activity in rats. Diabetologia 43:1512-1517
Preuss, J.M. and Goldie, R.G. (1999) Muscarinic cholinoceptor subtypes mediating tracheal smooth muscle contraction and inositol phosphate generation in guinea pig and rat. Eur. J. Pharmacol. 372:269-277
Scheen, A.J. and Lefebvre, P.J. (1999) Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes. Diabetes Care 22:1568-1577
Toyota, T. and Ueno, Y. (2000) Clinical effect and side effect of troglitazone. Nippon. Rinsho. 58: 376-382
Weidmann, P., Boehlen, L.M. and de Courten, M. (1993) Pathogenesis and treatment of hypertension associated with diabetes mellitus. Am. Heart. J., 125: 1498-1513
孫伯玉,方劑學,國立編譯館 出版,第170-173頁,1980。
何東燦、邱年永、馬建中等編,中醫內科學,國立編譯館 出版,第319-324頁,1986。
楊向輝,金匱要略注釋,國立編譯館 出版,第167-177頁,1986。
張伯臾,中醫內科學,知音出版社 出版,第564-568頁,1989。
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top