(3.234.221.162) 您好!臺灣時間:2021/04/14 16:09
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:::

我願授權國圖
: 
twitterline
研究生:倪曼婷
研究生(外文):Man-Ting Nee
論文名稱:枷羅木醇於streptozotocin誘發糖尿病大鼠之抗糖尿病作用
論文名稱(外文):The anti-diabetic effects of linalool on streptozotocin-induced diabetic rats
指導教授:劉承慈
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:營養學系碩士班
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:99
相關次數:
  • 被引用被引用:0
  • 點閱點閱:186
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
糖尿病 (DM)為國人常見慢性病之一,患者有胰島細胞功能衰竭及胰島素阻抗問題,並會發展出腎功能損傷。過去我們已證實台灣特有之土肉桂 (Cinnamomum osmophloeum Kaneh.),其枷羅木醇型之葉精油 (TC) 可抗DM,本研究目的為觀察其主要成分—枷羅木醇 (linalool, LIN)之抗DM作用。實驗以STZ (65 mg/kg BW, i.v.) 誘發大鼠DM後,隔日灌食LIN (1、5、10 mg/kg BW,分別為 LIN-L、LIN-M、LIN-H組),共灌食八次,並與土肉桂葉精油 (13 mg/kg BW)之作用比較。誘發後第十天進行胰島素耐受測試 (ITT),第十七天則進行葡萄糖耐受測試 (OGTT),誘發後二十一天犧牲並採其血液及臟器進行胰島素濃度、脂質過氧化程度、抗氧化分子濃度與酵素活性、促發炎激素含量及腎功能影響之測定。結果顯示,於ITT中灌食LIN及TC的DM大鼠,其血糖下降百分比均顯著獲得改善,且在OGTT期間之血糖變化曲線下面積,在灌食TC之DM大鼠血糖改善程度與灌食低及中劑量LIN者相當而高劑量LIN效果則優於TC。所有劑量LIN及TC均以相似程度改善HOMA-IR指數。在抗氧化作用方面,LIN及TC均有效改善骨骼肌、腎臟、肝臟及胰臟中脂質過氧化程度,並增加抗氧化分子 (GSH)含量及酵素 (GPx、GRd、SOD、CAT)活性。在抗發炎作用方面,LIN及TC降低骨骼肌、腎臟、肝臟及胰臟中IL-1β、IL-6及TNF-α之含量,並於骨骼肌、腎臟、肝臟、胰臟及血中皆可以降低NO的含量。LIN及 TC在腎功能測定方面,則可以改善白蛋白尿並逆轉DM致使的BUN、GFR上升。由本研究結果得知LIN及TC確實具有改善高血糖、胰島素阻抗及腎臟功能之作用,且至少部分歸因於改善氧化壓力及發炎作用。而本研究可說明枷羅木醇型土肉桂葉精油之抗DM作用至少有部分來自於其主要成分LIN。

Diabetes mellitus (DM) is a common chronic disease all over the world. Patients with DM suffer from islet cell failure and insulin resistance and will develop complications including renal damage. Previously, we have demonstrated an anti-diabetic activity of leave essential oil of linalool type Cinnamomum osmophloeum Kaneh (TC). The aim of the present study is to investigate the anti-diabetic activity of linalool (LIN), the major composition of TC. Male Wistar rats were injected with Streptozotocin (65 mg/kg BW, i.v.) to induce DM and received LIN (1, 5, 10 mg/kg BW), TC (13 mg/kg BW) or vehicle (corn oil, 2 ml/kg BW) every other day for eight times. Insulin tolerance test (ITT) was carried out at 10 days and oral glucose tolerance test (OGTT) was carried out at 17 days after induction. Rats were sacrificed on day 21 after the induction.We found all tested doses of LIN and TC to ameliorate fasting blood glucose level, insulin tolerance, glucose tolerance, and HOMA-IR. As to the antioxidative effect, LIN and TC decreased TBARS, increased the content of GSH and the activities of GPx, GRd, SOD and CAT in skeletal muscle, kidney, liver, and pancreas. LIN and TC also significantly reversed levels of IL-1β, IL-6 and TNF-αin skeletal muscle, kidney, liver, and pancreas of DM rats, and decreased the level of NO in peripheral blood from DM rats. Both BUN and GFR in DM rats were ameliorated by LIN and TC suggesting ameliorated renal disorder.In conclusion, LIN and TC improved hyperglycemia and insulin resistance, and attenuated the development of diabetic nephropathy in association with ameliorated oxidative stress and inflammatory condition in DM. The antidiabetic effects of linalool type Cinnamomum osmophloeum Kaneh showed to be at leased partly exerted through its major composition, LIN.

圖次表………………………………………………………………………………I
中英文專有名詞及縮寫對照………………………………………………………III
中文摘要……………………………………………………………………………V
英文摘要……………………………………………………………………………VI

第一章、文獻探討…………………………………………………………………1
壹、 緒論………………………………………………………………………1
貳、 糖尿病診斷與分類………………………………………………………2
一、 糖尿病概述…………………………………………………………2
二、 糖尿病診斷及分類…………………………………………………2
參、 糖尿病併發之腎病變……………………………………………………7
一、 糖尿病腎病變………………………………………………………7
二、 糖尿病腎臟病的診斷與分期………………………………………8
肆、 糖尿病進行及其併發症發展之相關機制………………………………10
一、 氧化壓力與糖尿病自然史…………………………………………10
二、 氧化壓力與糖尿病併發症發展……………………………………12
三、 發炎反應與糖尿病自然史…………………………………………13
四、 發炎反應與糖尿病併發症發展……………………………………16
伍、已知台灣土肉桂葉精油及枷羅木醇之生物學活性…………………………17
一、台灣土肉桂葉精油介紹…………………………………………………17
二、我們過去製備之枷羅木醇型土肉桂葉精油之成分及其生物學活性之介紹………………………………………………………………………………17
陸、研究動機與目的………………………………………………………………21
第二章、材料與方法………………………………………………………………22
壹、 實驗材料與儀器…………………………………………………………22
一、 化學試藥……………………………………………………………22
二、 分析套組……………………………………………………………24
三、 儀器設備……………………………………………………………24
四、 試劑配置……………………………………………………………25
五、 實驗動物……………………………………………………………25
貳、 動物實驗方法……………………………………………………………26
一、 糖尿病動物模式建立………………………………………………26
二、 試劑之灌食…………………………………………………………26
三、 動物之處理…………………………………………………………26
四、 胰島素耐受測試……………………………………………………27
五、 口服葡萄糖耐受測試………………………………………………28
六、 樣品製備……………………………………………………………28
參、 生化分析…………………………………………………………………30
一、 脂質過氧化程度分析………………………………………………30
二、 總麩胱甘肽含量測定………………………………………………31
三、 抗氧化酵素活性測定………………………………………………32
四、 Cytokines含量測定………………………………………………37
五、 一氧化氮衍生物含量測定…………………………………………44
六、 胰島素含量測定……………………………………………………46
七、 尿素氮含量測定……………………………………………………47
八、 肌酸酐含量測定……………………………………………………48
九、 白蛋白含量測定……………………………………………………49
十、 蛋白質濃度測定……………………………………………………50
肆、 指數計算…………………………………………………………………52
一、 口服葡萄糖耐受性試驗血糖變化曲線下面積計算………………52
二、 胰島素阻抗指數計算………………………………………………52
三、 肌酸肝廓清率計算…………………………………………………52
四、 腎絲球過濾率計算…………………………………………………52
伍、統計分析………………………………………………………………………53

第三章、結果………………………………………………………………………54
壹、 正常大鼠與糖尿病大鼠之生長代謝值與血糖之差異…………………54
貳、 枷羅木醇對於糖尿病大鼠生長代謝值之影響…………………………54
參、 枷羅木醇對於糖尿病大鼠空腹血糖值之影響…………………………55
肆、 枷羅木醇對於糖尿病大鼠臟器與體重百分比之影響…………………55
伍、 枷羅木醇對於糖尿病大鼠胰島素濃度之影響…………………………56
陸、 枷羅木醇對於糖尿病大鼠胰島素敏感性之影響………………………56
柒、 枷羅木醇對於糖尿病大鼠葡萄糖耐受程度之影響……………………57
捌、 枷羅木醇對於糖尿病大鼠脂質過氧化程度及抗氧化系統之影響……57
玖、 枷羅木醇對於糖尿病大鼠發炎反應之影響……………………………60
壹拾、枷羅木醇對於糖尿病大鼠腎臟功能之影響………………………………62

第四章、討論………………………………………………………………………84
壹、枷羅木醇對於糖尿病大鼠生長代謝值之影響………………………………84
貳、枷羅木醇對於糖尿病大鼠空腹血糖值與胰島素濃度之影響………………85
參、枷羅木醇對於糖尿病大鼠胰島素敏感性及葡萄糖耐受程度之影響………85
肆、枷羅木醇對於糖尿病大鼠臟器與體重百分比之影響………………………87
伍、枷羅木醇對於糖尿病大鼠脂質過氧化程度及抗氧化系統之影響…………88
陸、枷羅木醇對於糖尿病大鼠發炎反應之影響…………………………………89
柒、枷羅木醇對於糖尿病大鼠腎臟功能之影響…………………………………91

第五章、結論………………………………………………………………………93
參考文獻……………………………………………………………………………94


Association, A. D. (2013). "Diagnosis and classification of diabetes mellitus." Diabetes Care 36(Suppl 1): S67-S74.
 Abu El-Asrar, A. M., et al. (2013). "High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina." Mediators Inflamm 2013: 863036.
 Albareda, M., et al. (2000). "Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test." Diabetologia 43(12): 1507-1511.
 Ballabeni, V., et al. (2010). "Ocotea quixos Lam. essential oil: in vitro and in vivo investigation on its anti-inflammatory properties." Fitoterapia 81(4): 289-295.
 Banerjee, S., et al. (1995). "Modulatory influence of camphor on the activities of hepatic carcinogen metabolizing enzymes and the levels of hepatic and extrahepatic reduced glutathione in mice." Cancer letters 88(2): 163-169.
 Bernhart, F., et al. (1961). Glucose uptake by epididymal fat pads from rats fed glucose, lactose or a glucose-galactose mixture. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, NY), Royal Society of Medicine.
 Chakraborty, C., et al. (2011). "Landscape mapping of functional proteins in insulin signal transduction and insulin resistance: a network-based protein-protein interaction analysis." PLoS One 6(1): e16388.
 Chao, L. K., et al. (2008). "Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling." Food Chem Toxicol 46(1): 220-231.
 Cheng, S. S., et al. (2006). "Chemical polymorphism and antifungal activity of essential oils from leaves of different provenances of indigenous cinnamon (Cinnamomum osmophloeum)." Bioresour Technol 97(2): 306-312.
 Celik, S. and A. Ozkaya (2002). "Effects of intraperitoneally administered lipoic acid, vitamin E, and linalool on the level of total lipid and fatty acids in guinea pig brain with oxidative stress induced by H2O2." J Biochem Mol Biol 35(6): 547-552.
 Di Virgilio, F. (2013). "The therapeutic potential of modifying inflammasomes and NOD-like receptors." Pharmacol Rev 65(3): 872-905.
 Deepa, B. and C. Venkatraman Anuradha (2013). "Effects of linalool on inflammation, matrix accumulation and podocyte loss in kidney of streptozotocin-induced diabetic rats." Toxicol Mech Methods 23(4): 223-234.
 Deepa, B. and C. V. Anuradha (2011). "Linalool a plant derived monoterpene alcohol rescues kidney from diabetes-induced nephropathic changes via blood glucose reduction." Diabetologia Croatica 40(4): 121.
 Dezayee, Z. M. (2011). "Interleukin-18 can predict pre-clinical atherosclerosis and poor glycemic control in type 2 diabetes mellitus." Int J Appl Basic Med Res 1(2): 109-112.
 Devaraj, S., et al. (2006). "Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes." Diabetes 55(3): 774-779.
 Dandona, P., et al. (2004). "Inflammation: the link between insulin resistance, obesity and diabetes." Trends in immunology 25(1): 4-7.
 Edalat, B., et al. (2013). "Association of metabolic syndrome with inflammatory mediators in women with previous gestational diabetes mellitus." J Diabetes Metab Disord 12(1): 8.
 Elsner, M., et al. (2000). "Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin." Diabetologia 43(12): 1528-1533.
 Elliott, W. C., et al. (1985). "Experimental gentamicin nephrotoxicity: effect of streptozotocin-induced diabetes." Journal of Pharmacology and  Experimental Therapeutics 233(1): 264-270.
 Fradkin, J. E. and G. P. Rodgers (2013). "Diabetes research: a perspective from the National Institute of Diabetes and Digestive and Kidney Diseases." Diabetes 62(2): 320-326.
 Feng, L., et al. (2013). "Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-kappaB pathway activation in human umbilical vein endothelial cells." J  Ethnopharmacol 148(1): 27-36.
 Guedes, E. P., et al. (2013). "Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment." Diabetol Metab Syndr 5(1): 25.
 Guo, R., et al. (2013). "The protective effect of fasudil on the structure and function of cardiac mitochondria from rats with type 2 diabetes induced by streptozotocin with a high-fat diet is mediated by the attenuation of oxidative stress." Biomed Res Int 2013: 430791.
 Gong, Z. and R. H. Muzumdar (2012). "Pancreatic function, type 2 diabetes, and metabolism in aging." Int J Endocrinol 2012: 320482.
 Ghule, A. E., et al. (2012). "Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats." Int Immunopharmacol 14(4): 740-748.
 Goldberg, R. B. (2009). "Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications." Journal of Clinical Endocrinology & Metabolism 94(9): 3171-3182.
 Hu, J., et al. (2013). "Long term effects of the implantation of Wharton''s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus." Endocr J 60(3): 347-357.
 Huo, M., et al. (2013). "Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model." J Surg Res 180(1): e47-54.
 He, Q., et al. (2012). "HMGB1 promotes the synthesis of pro-IL-1beta and pro-IL-18 by activation of p38 MAPK and NF-kappaB through receptors for advanced glycation end-products in macrophages." Asian Pac J Cancer Prev 13(4): 1365-1370.
 He, L. J., et al. (2009). "Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action." J Endocrinol 200(3): 347-355.
 Kemmochi, Y., et al. (2013). "Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Lepr (fa) Rat: A New Obese Type 2 Diabetic Model." J Diabetes Res 2013: 948257.
 Karunakaran, U. and K. G. Park (2013). "A systematic review of oxidative stress and safety of antioxidants in diabetes: focus on islets and their defense." Diabetes Metab J 37(2): 106-112.
 Kumawat, M., et al. (2013). "Antioxidant Enzymes and Lipid Peroxidation in Type 2 Diabetes Mellitus Patients with and without Nephropathy." N Am J Med Sci 5(3): 213-219.
 Kumar, S., et al. (2012). "GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats." Cardiovasc Diabetol 11: 95.
 Kaneto, H., et al. (2004). "Involvement of oxidative stress and the JNK pathway in glucose toxicity." Rev Diabet Stud 1(4): 165-174.
 Kramer, H. J., et al. (2003). "Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus." JAMA: the journal of the American Medical Association 289(24): 3273-3277.
 Lee, S. C., et al. (2013a). "Chemical Composition and Hypoglycemic and Pancreas-Protective Effect of Leaf Essential Oil from Indigenous Cinnamon ( Cinnamomum osmophloeum Kanehira)." J Agric Food Chem 61(20): 4905-4913.
  Lee, H. M., et al. (2013b). "Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes." Diabetes 62(1): 194-204.
Lim, A. K. and G. H. Tesch (2012). "Inflammation in diabetic nephropathy." Mediators Inflamm 2012: 146154.
 Lin, S. S., et al. (2011). "In vivo cytokine modulatory effects of cinnamaldehyde, the major constituent of leaf essential oil from Cinnamomum osmophloeum Kaneh." Phytother Res 25(10): 1511-1518.
Leung, K. (2004). 99mTc-Interleukin-18-binding protein-Fc-interlukin-1 receptor antagonist. Molecular Imaging and Contrast Agent Database (MICAD). Bethesda MD.
 Lee, H.-S. (2002). "Inhibitory activity of Cinnamomum cassia bark-derived component against rat lens aldose reductase." J Pharm Pharm Sci 5(3): 226-230.
 Lake, B. G., et al. (1989). "Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites." Toxicology and applied pharmacology 97(2): 311-323.
 Leevy, C. M., et al. (1950). "Diabetes mellitus and liver dysfunction: etiologic and therapeutic considerations." The American Journal of Medicine 8(3): 290-299.
 McArdle, M. A., et al. (2013). "Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies." Front Endocrinol (Lausanne) 4: 52.
 Misbah, H., et al. (2013). "Antidiabetic and antioxidant properties of Ficus deltoidea fruit extracts and fractions." BMC Complement Altern Med 13: 118.
 Maeda, H., et al. (2013). "Kuromoji (Lindera umbellata) essential oil inhibits LPS-induced inflammation in RAW 264.7 cells." Biosci Biotechnol Biochem 77(3): 482-486.
 Mahmoud, M. F., et al. (2013). "Quercetin Protects against Diabetes-Induced Exaggerated Vasoconstriction in Rats: Effect on Low Grade Inflammation." PLoS One 8(5): e63784.
 Marble, A., et al. (1938). "Enlargement of the Liver in Diabetic Children: I. Its Incidence, Etiology and Nature." Archives of Internal Medicine 62(5): 740.
 Nogueira-Machado, J. A. and C. M. de Oliveira Volpe (2012). "HMGB-1 as a target for inflammation controlling." Recent Pat Endocr Metab Immune Drug Discov 6(3): 201-209.
 Nin, J. W., et al. (2012). "Higher plasma high-mobility group box 1 levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12 year follow-up study." Diabetologia 55(9): 2489-2493.
 Okazaki, K. and T. Chiba (2002). "Autoimmune related pancreatitis." Gut 51(1): 1-4.
 Pattanayak, P., et al. (2010). "Ocimum sanctum Linn. A reservoir plant for therapeutic applications: An overview." Pharmacogn Rev 4(7): 95-105.
 Park, S. W., et al. (2009). "Excessive loss of skeletal muscle mass in older adults with type 2 diabetes." Diabetes Care 32(11): 1993-1997.
 Peana, A. T., et al. (2006). "(-)-Linalool inhibits in vitro NO formation: Probable involvement in the antinociceptive activity of this monoterpene compound." Life Sci 78(7): 719-723.
 Quintans-Junior, L. J., et al. (2013). "beta-Cyclodextrin-complexed (-)-linalool produces antinociceptive effect superior to that of (-)-linalool in experimental pain protocols." Basic Clin Pharmacol Toxicol.
 Rodriguez-Hernandez, H., et al. (2013). "Obesity and inflammation: epidemiology, risk factors, and markers of inflammation." Int J Endocrinol 2013: 678159.
 Rock, K. L., et al. (2013). "Uric acid as a danger signal in gout and its comorbidities." Nat Rev Rheumatol 9(1): 13-23.
 Shao, N., et al. (2013). "Relationship between Oxidant/Antioxidant Markers and Severity of Microalbuminuria in the Early Stage of Nephropathy in Type 2 Diabetic Patients." J Diabetes Res 2013: 232404.
 Shibata, T., et al. (2013). "Inhibition of the TNF-alpha-Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR." J Pharmacol Sci.
 Soetikno, V., et al. (2011). "Curcumin ameliorates macrophage infiltration by inhibiting NF-kappaB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy." Nutr Metab (Lond) 8(1): 35.
 Subash, B. P., et al. (2007). "Cinnamaldehyde--a potential antidiabetic agent." Phytomedicine: international journal of phytotherapy and phytopharmacology 14(1): 15.
 Stadler, M., et al. (2006). "Long-term mortality and incidence of renal dialysis and transplantation in type 1 diabetes mellitus." J Clin Endocrinol Metab 91(10): 3814-3820.
 Takada, J., et al. (2007). "Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass." Metabolism 56(7): 977-984
 Thomson, S. C., et al. (2001). "Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes." Journal of Clinical Investigation 107(2): 217-224.
 van Greevenbroek, M. M., et al. (2013). "Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences." Neth J Med 71(4): 174-187.
 Virmani, A. and A. Kulkarni (2012). "Diabetes in young: Beyond type 1." Indian J Endocrinol Metab 16(Suppl 2): S256-258.
 Wang, C., et al. (2012). "Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation." PLoS One 7(6): e38285.
 Yang, C.-S., et al. (2012). "The role of NLR-related protein 3 inflammasome in host defense and inflammatory diseases." International neurourology journal 16(1): 2-12.
 Zhang, W., et al. (2013). "The Protective Effects of Beta-Casomorphin-7 against Glucose -Induced Renal Oxidative Stress In Vivo and Vitro." PLoS One 8(5): e63472.
行政院衛生署統計處 (2012),國民十大死因統計結果
行政院農委會 (2010),土肉桂種子發芽與儲藏之研究
台灣糖尿病衛教學會 (2012),糖尿病腎臟病變
台灣糖尿病衛教學會 (2012),糖尿病的藥物治療
台灣糖尿病衛教學會 (2012),糖尿病的疾病生理學及流行病學
楊政川 (2010),台灣森林特產物-土肉桂



QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
系統版面圖檔 系統版面圖檔