跳到主要內容

臺灣博碩士論文加值系統

(44.192.38.248) 您好!臺灣時間:2022/11/30 22:37
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:劉欣茹
研究生(外文):Hsin-Ru Liu
論文名稱:正常血糖治療後可恢復早期糖尿病大鼠壓感反射功能失調
論文名稱(外文):Euglycemic therapy restores baroreflex dysfunction in rats with early diabetes
指導教授:張懷仁
指導教授(外文):Huai-Ren Chang
口試委員:劉安邦吳賢財
口試委員(外文):An-Bang LiuHsien-Tsai Wu
口試日期:2015-07-28
學位類別:碩士
校院名稱:慈濟大學
系所名稱:生理暨解剖醫學碩士班
學門:醫藥衛生學門
學類:醫學學類
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:47
中文關鍵詞:壓感反射自主神經糖尿病自發性壓感反射高血糖
外文關鍵詞:Baroreflex sensitivityautonomic nerve functiondiabetesspontaneous baroreflexhyperglycemia
相關次數:
  • 被引用被引用:0
  • 點閱點閱:275
  • 評分評分:
  • 下載下載:6
  • 收藏至我的研究室書目清單書目收藏:0
糖尿病伴隨著自主神經功能失調,是糖尿病患者發病率及死亡率的主要原因。動脈壓力反射敏感性(Baroreflex sensitivity, BRS)用於評估心臟自主功能之指標,已知在糖尿病前期和糖尿病會受損,自主神經功能失調與糖尿病的高血糖為其致病因子。在本研究中,我們以鏈佐菌素(streptozotocin, STZ)誘導的糖尿病大鼠來評估BRS和心率變異性的變化。本實驗使用20隻成年雄性Wistar Kyoto(WKY)大鼠(8週齡)腹腔注射STZ誘導糖尿病,再以21隻age-match的雄性WKY大鼠腹腔注射等量生理鹽水後作為對照組。所有的動物在一週後接受血糖檢測,約在10~12週即可誘發成糖尿病大鼠(血糖> 250 mg/dL)。心電圖和動脈血壓透過血壓感測器植入右股動脈,記錄30分鐘後,接著動物以傳統藥理方式靜脈注射phenylephrine來評估BRS。糖尿病大鼠接受皮下注射胰島素,待其血糖低於200 mg/dL,當血糖恢復正常狀態時進行相同的記錄。藥物誘發BRSdrug在早期糖尿病高血糖時期是檢測不到,在正常血糖狀態則出現,趨近於正常鼠。同時,相較於正常情況下以spontaneous sequencing technique觀察 BRS的變化,BRSspt在早期糖尿病高血糖時期會下降,經胰島素治療後會上升,統計上為無意義的。LHR在高血糖狀態下降而胰素治療後上升,與對照組相比有統計上差異(p <0.05)。在這項研究中,我們設計了一組以靜脈注射葡萄糖水的大鼠,藉由測量BRSdrug,BRSspt和LHR,證明壓感反射功能失調並非單由高血糖造成而是糖尿病病程的發展所致,當血糖恢復正常的狀態時,則受損的壓感反射有明顯回復的現象。
Diabetes-associated autonomic dysfunction is one of the major causes of mortality and morbidity in diabetic patients. Arterial baroreflex sensitivity (BRS), an index of cardiac autonomic function, was impaired in prediabetes and diabetes. Hyperglycemia has been implicated as a pathogenic factor for diabetic autonomic dysfunction. In this study, we assessed the changes of BRS and heart rate variability (HRV) in experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin in 20 adult male Wistar Kyoto (WKY) rats (aged 8 weeks). Twenty-one age-matched male WKY rats were used as control after intraperitoneal injection of same amount of normal saline. All the animals received weekly check of blood sugar. Diabetes mellitus (blood sugar >250mg/dL) occurred 10~12 weeks after the induction. ECG was recorded with subcutaneous electrodes and arterial blood pressure were acquired via intra-arterial implantation of a tonometry in the right femoral artery. After 30-minute recording, the animals received intravenous injection of phenylephrine for traditional pharmacological assessment of BRS (BRSdrug). After a complete recording, the rats received subcutaneous injection of insulin till the blood sugar below 200 mg/dL, then received similar assessment at euglycemic state. The BRSdrug were undetectable at hyperglycemic state then approached to the values of the normal rats at euglycemic state. Similar changes of BRS were noted on the BRS measured by spontaneous sequencing technique. Meanwhile, HRV indicated as low frequency power to high frequency power ratio (LHR) by fast Fourier transform, also decreased at hyperglycemic state than increased after insulin treatment although there is no statistic significance. On the other hand, animals received intravenous injection of glucose water to get a hyperglycemic state did not have similar changes of BRS. However, the hyperglycemic rats had higher LHR as compared with the normal did. In this study, we demonstrated that autonomic dysfunction and impaired baroreflex activity occurs in early diabetes can be restored by insulin therapy, additionally, the changes may be caused by diabetes process but hyperglycemia per se.
目錄
中文摘要 III
Abstract IV
1.1 前言 1
1.2 自主神經 1
1.3 人體的壓感反射(Baroreflex) 2
1.4 研究動機與目的 3
第二章、材料與方法 5
2.1 一般實驗動物的備置 5
2.2 實驗設計及流程 5
2.3心電圖(Electrocardiogram, ECG)原理及信號擷取方法 6
2.4自發性的壓力反射敏感性(Spontaneous baroreflex sensitivity, BRS)測量方法 9
2.5 系統說明 11
2.6 統計方法 11
第三章、實驗結果與分析 12
3.1 基本生理參數的比較 12
3.2 以傳統藥理學進行壓感反射敏感性評估 13
3.3 大鼠以兩種不同方式測量BRS的結果分析 13
3.4 正常鼠與糖尿病鼠HRV分析 14
3.5 高血糖對BRS機制造成的影響 14
3.6 正常大鼠以靜脈注射葡萄糖水藉由傳統藥理學進行壓感反射敏感性評估 15
3.7 靜脈注射葡萄糖水大鼠以兩種不同方式測量BRS的結果分析 15
3.8 靜脈注射葡萄糖水大鼠HRV分析 15
第四章 討論 17
第五章 未來展望 19

圖目錄
圖一、壓感反射負回饋循環示意圖 20
圖二、WKY大鼠在麻醉情況下進行手術處理及監測生理訊號 20
圖三、壓感反射係數之測量流程 21
圖四、R-R interval 序列 21
圖五、心肌細胞動作電位與心電圖(electrocardiogram, ECG)波型 22
圖六、壓感反射敏感性的自發性序列分析法 22
圖七、自發性壓感反射敏感性以spontaneous sequence method演算法之流程圖 23
圖八、動物模型測量系統概念圖 24
圖九、正常大鼠與早期糖尿病大鼠藉由靜脈注射升壓藥物誘發的壓感反射敏感性 25
圖十、正常大鼠與糖尿病大鼠BRS統計圖 26
圖十一、正常大鼠與早期糖尿病大鼠HRV評估自主神經之頻譜圖 27
圖十二、正常鼠與糖尿病鼠LHR統計圖 28
圖十三、正常大鼠、早期糖尿病大鼠與靜脈注射葡萄糖水的大鼠以傳統藥理學的方式評估BRS 29
圖十四、正常大鼠、糖尿病大鼠與靜脈注葡萄糖水的大鼠BRS統計圖 30
圖十五、靜脈注射葡萄糖水大鼠HRV評估自主神經之頻譜圖 31
圖十六、靜脈注射葡萄糖水大鼠LHR統計圖 32

表目錄
表一、 2011年到2014 年國人十大死因百分比 33
表二、 心電圖十二導程 34
表三、正常大鼠與糖尿病大鼠及胰島素治療後之各項生理參數 35
表四、 正常大鼠與糖尿病大鼠和靜脈注射葡萄糖水的高血糖時期之各項生理參數 36


參考文獻

Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ (1981) Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220-222.

Aktug H, Uysal A, Yavasoglu A, Oltulu F, Akarca SO, Yilmaz-Dilsiz O, Oktem G (2013) The detrimental effects of diabetes on pluripotency determined by KLF4, SOX2, C-MYC and OCT4 immunoreactivity in rat testes. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 22:327-335.

Beitzke M, Pfister P, Fortin J, Skrabal F (2002) Autonomic dysfunction and hemodynamics in vitamin B12 deficiency. Auton Neurosci 97:45-54.

Bertinieri G, di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G (1985) A new approach to analysis of the arterial baroreflex. J Hypertens Suppl 3:S79-81.

Dall'Ago P, Fernandes TG, Machado UF, Bello AA, Irigoyen MC (1997) Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats. Braz J Med Biol Res 30:119-124.

Dall'ago P, D'Agord Schaan B, da Silva VO, Werner J, da Silva Soares PP, de Angelis K, Irigoyen MC (2007) Parasympathetic dysfunction is associated with baroreflex and chemoreflex impairment in streptozotocin-induced diabetes in rats. Auton Neurosci 131:28-35.

Eckberg DL (1980) Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol 239:H581-593.

Eric P. Widmaier HR, Kevin T. Strang (2013) Vander's Human Physiology: The Mechanisms of Body Function, 12/e. McGraw-Hill international Enterprises LLC.

Fazan R, Jr., Ballejo G, Salgado MC, Moraes MF, Salgado HC (1997) Heart rate variability and baroreceptor function in chronic diabetic rats. Hypertension 30:632-635.

Frattola A, Parati G, Gamba P, Paleari F, Mauri G, Di Rienzo M, Castiglioni P, Mancia G (1997) Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus. Diabetologia 40:1470-1475.
Gindea AJ, Slater J, Kronzon I (1990) Doppler echocardiographic flow velocity measurements in the superior vena cava during the Valsalva maneuver in normal subjects. Am J Cardiol 65:1387-1391.

Gribbin B, Pickering TG, Sleight P, Peto R (1971) Effect of age and high blood pressure on baroreflex sensitivity in man. Circ Res 29:424-431.

Huber DA, Carmo JM, Castania JA, Fazan R, Jr., Salgado HC (2007) Does acute hyperglycemia alter rat aortic depressor nerve function? Braz J Med Biol Res 40:1567-1576.

La Rovere MT, Bigger JT, Jr., Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351:478-484.

Lefrandt JD, Mulder MC, Bosma E, Smit AJ, Hoogenberg K (2000) Inverse relationship between blood glucose and autonomic function in healthy subjects. Diabetes Care 23:1862-1864.

Liu AJ, Ma XJ, Shen FM, Liu JG, Chen H, Su DF (2007) Arterial baroreflex: a novel target for preventing stroke in rat hypertension. Stroke 38:1916-1923.

Ludbrook J, Mancia G, Ferrari A, Zanchetti A (1977) The variable-pressure neck-chamber method for studying the carotid baroreflex in man. Clin Sci Mol Med 53:165-171.

Maeda CY, Fernandes TG, Timm HB, Irigoyen MC (1995) Autonomic dysfunction in short-term experimental diabetes. Hypertension 26:1100-1104.

Marfella R, Nappo F, De Angelis L, Paolisso G, Tagliamonte MR, Giugliano D (2000) Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients. Diabetes Care 23:658-663.

Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, Pozzoli M, Opasich C, Tavazzi L (1997) Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation 96:3450-3458.

Nishimura RA, Tajik AJ (1986) The Valsalva maneuver and response revisited. Mayo Clin Proc 61:211-217.

Osculati G, Grassi G, Giannattasio C, Seravalle G, Valagussa F, Zanchetti A, Mancia G (1990) Early alterations of the baroreceptor control of heart rate in patients with acute myocardial infarction. Circulation 81:939-948.

Pagani M, Somers V, Furlan R, Dell'Orto S, Conway J, Baselli G, Cerutti S, Sleight P, Malliani A (1988a) Changes in autonomic regulation induced by physical training in mild hypertension. Hypertension 12:600-610.

Pagani M, Malfatto G, Pierini S, Casati R, Masu AM, Poli M, Guzzetti S, Lombardi F, Cerutti S, Malliani A (1988b) Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy. J Auton Nerv Syst 23:143-153.

Parlow J, Viale JP, Annat G, Hughson R, Quintin L (1995) Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses. Hypertension 25:1058-1068.

Ruiz J, Monbaron D, Parati G, Perret S, Haesler E, Danzeisen C, Hayoz D (2005) Diabetic neuropathy is a more important determinant of baroreflex sensitivity than carotid elasticity in type 2 diabetes. Hypertension 46:162-167.

Shih CD, Kuo DH, Huang CW, Gu YH, Chen FA (2008) Autonomic nervous system mediates the cardiovascular effects of Rhodiola sacra radix in rats. J Ethnopharmacol 119:284-290.

Skrapari I, Tentolouris N, Katsilambros N (2006) Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome. Current diabetes reviews 2:329-338.

Smyth HS, Sleight P, Pickering GW (1969) Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. Circ Res 24:109-121.

Yang CH, Shyr MH, Kuo TB, Tan PP, Chan SH (1995) Effects of propofol on nociceptive response and power spectra of electroencephalographic and systemic arterial pressure signals in the rat: correlation with plasma concentration. J Pharmacol Exp Ther 275:1568-1574.

行政院衛生福利部統計處 “國人十大死因統計,” 2014. Available: http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=1601.
翁根本 何慈育, 歐善福, 林竹川, 謝凱生 (2009) 心律變動性分析. 台灣醫學 52:290-293.

陳慶順 (民國101年七月) 高血壓大鼠血管內皮功能及自主神經調控功能之評估, 國立東華大學電機工程學系碩士論文.

葉容任 (民國103年七月) 利用二進制編碼描繪心跳間隔和血壓訊號震盪以評估壓感反射及其應用, 國立東華大學電機工程學系碩士論文.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊