臺灣博碩士論文加值系統

敗血症的高死亡率一直是臨床上的難題，由於其病程發展快速，病理機轉複雜，在治療上實有其難以掌握之處。敗血症發生後，無法控制的細胞激素風暴是病人死亡的重要原因，因此，發炎細胞激素與抗發炎細胞激素的變化是病情是否惡化的重要關鍵。爲了瞭解發炎細胞激素以及抗發炎細胞激素與死亡的相關性，本研究選擇介白素6與介白素10分別作為發炎細胞激素以及抗發炎細胞激素之代表，先以此2因子對於預後準確度進行評估，再以中藥作為治療之驗證工具。研究方法為老鼠於麻醉後先由尾動脈採血測得介白素6與介白素10之基準值，之後進行盲腸結紮及穿孔手術引發老鼠敗血症，第一部分為預後評估：35隻老鼠於手術後趨於平穩之基礎心跳倍率稱為1倍，在之後逐漸增加之心跳倍率（1.15倍、1.25倍以及1.35倍）下進行抽血檢測介白素6與介白素10，並觀察其3天存活率，將造型成功者依照存活或死亡分為兩組，以此兩細胞激素為因子做預後鑑別方程式，評估其準確度；第二部分為單味中藥石膏治療：72隻老鼠隨機分為3組，在手術後6小時分別給予高劑量石膏(2.7 cc/kg)、低劑量石膏(1.35 cc/kg)以及生理食鹽水(2.7 cc/kg)，評估其3天存活率，確定石膏較佳作用劑量之後，再取21隻老鼠隨機分為治療組（n=8）、控制組（n=8）與空白對照組（n=5），在手術後6小時分別給予石膏以及生理食鹽水，並且每4小時量測血壓與心跳以及抽血檢測介白素6與介白素10之數值；第三部分為中藥複方白虎湯治療：12隻老鼠隨機分為治療組（n=6）與控制組（n=6），手術後之實驗流程與石膏相同。第一部分結果顯示：介白素6的數值在死亡組隨著心跳倍率升高，數值持續上升，而存活組在1.15倍時數值雖然升高，但到了1.25倍時，即開始下降，到了1.35倍時繼續下降；介白素10亦有類似的趨勢，所不同的是到了1.25倍以及1.35倍時數值出現持平之現象。在心跳倍率1.15倍時其預後線性鑑別方程式鑑別率為68.33%；1.25倍以及1.35倍時，鑑別率分別可高至93.33%以及95.45%；第二部分結果顯示：石膏確實能有效降低敗血證老鼠之死亡率，而且對於介白素6的濃度有明顯降低之作用，至於介白素10雖無明顯降低效果但可看出其趨勢，至於血壓與心跳則無明顯作用；第三部分結果顯示：白虎湯與石膏之不同處在於對介白素6以及介白素10的濃度均有明顯降低作用。由以上結果可知：介白素6以及介白素10此兩因子對於敗血症的死亡有著重要的影響，是敗血症導致死亡的關鍵。因此，在未來的研究上，若能同時注重發炎細胞激素與抗發炎細胞激素的動態變化趨勢，進而給予及時並且正確的治療，應是一個值得深入的方向。

AbstractThe high mortality rate of sepsis is always a difficult problem to overcome in clinic. Because the course of sepsis is developed fast and the pathophisiology turns complicated, it is difficult to control in treating. After sepsis happens, the uncontrollable cytokine storm is the important reason of patient''s death, so the change of proinflammatory and anti-inflammatory cytokines is the important key whether the condition worsens. To understand the importance of proinflammatory and anti-inflammatory cytokines in mortality, the study chooses IL-6 and IL-10 to represent proinflammatory and anti-inflammatory cytokines respectively. We use these two factors to evaluate prognosis accuracy first, and then regard traditional Chinese medicine as verification tool in treatment. The baseline values of IL-6 and IL-10 were measured by collecting blood with mouse tail artery after anesthetizing. The first part is the evaluation of prognosis: 35 Sprague-Dawley rats, weighing in between 250 to 300g, underwent cecal ligation and puncture (CLP) procedures and femoral arterial catheterization. When the heart rates reached 1.15, 1.25 and 1.35 times that of the baseline heart rate, blood sampling was done for IL-6 and IL-10. The prognosis was followed up for 3 days after CLP, and all rats were then divided into survival or non-survival groups. Finally, the relationships among survival condition, heart rate, IL-6, and IL-10 were analyzed by two-way ANOVA and multiple comparison. A linear discriminant function for the prognosis of sepsis was developed by IL-6 and IL-10 at different heart rates. Second part: the treatment of single flavor traditional Chinese medicine gypsum: Seventy-two rats were randomly assigned to three groups: control group, low dose treatment group and high dose treatment group. Sepsis was induced by cecal ligation and puncture. After 6 h, control group received normal saline 2.7cc/kg, low dose and high dose treatment groups received Gypsum 1.35cc/kg and 2.7cc/kg respectively. We observed three days for survival rate analysis. To realize the mechanism of gypsum further, we developed three groups randomly: control group (n=8), the most effective group (n=8) and sham group (n=5). Normal saline or gypsum was given subcutaneously 6h later. Inflammatory cytokines IL-6 and IL-10 were measured before CLP and every 4 h after CLP for 24 h. Blood pressure and heart rate were also measured every 4 h after CLP for 24 h. The third part: to realize the mechanism of Pai-hu-tang further, we developed two groups randomly: control group (n=6) and treatment group (n=6). Normal saline or Pai-hu-tang was given subcutaneously 6h later. Inflammatory cytokines IL-6 and IL-10 were measured before CLP and every 4 h after CLP for 24 h. Blood pressure and heart rate were also measured every 4 h after CLP for 24 h. The result shows: First part: IL-6 elevated continuously with the increment of the heart rate in the non-survival group, but in the survival group, the IL-6 elevation started to fall when the heart rate reached 1.25 times; a similar trend was found in the change of IL-10. The prediction rate was 68.33% when the heart rate reached 1.15 times, and increased to 93.33% and 95.45% when heart rates reached 1.25 and 1.35 times respectively. Second part: 3-day survival rate in both treatment groups were higher than the control group. IL-6 levels were significantly higher in the control than in the treatment group at 12 h,16 h,20 h and 24 h. Though there was no significant difference between control and treatment groups, the IL-10 levels seemed to have a decreasing trend in the treatment group. There was no obvious increase in blood pressure among these three groups. Heart rate increased by time in control and treatment groups and had significant difference with sham group at 16 h, 20 h and 24 h. Third part: IL-6 levels were significantly higher in the control than in the treatment group at 12 h, 16 h,20 h and 24 h. IL-10 levels were significantly higher in the control than in the treatment group at 16 h, 20 h and 24 h. Conclusion: IL6 and IL10 are very effective to the mortality of sepsis. They are strongly correlated to the pathogenesis and treatment of sepsis. In the future, if we can pay attention to the dynamic change of these two cytokines, it may be valuable in the treatment of sepsis.

目　　錄
第一章　前言 1
第二章　文獻探討 3
壹、現代醫學有關敗血症之論述 3
一、定義 3
二、病因 4
三、病理機轉 6
四、治療 9
五、預後評估 11
貳、傳統中醫有關敗血症之論述 18
一、敗血症 18
二、嚴重敗血症 19
三、敗血性休克 22
參、溫病氣分證用藥文獻探討 24
一、氣分證各類型分析 24
二、白虎湯組成 25
三、白虎湯個別藥物探討 26
肆、敗血症動物模型討論 28
一、內毒素模型 28
二、敗血症模型 29
三、盲腸結紮以及穿孔簡介 30
第三章　材料與方法 32
壹、實驗設計 32
貳、實驗動物 32
參、實驗儀器設備與試劑 32
一、手術器具 32
二、實驗試劑 33
三、實驗儀器 34
四、中藥基源鑑定及製備 34
肆、敗血症造型成功評估 35
一、血液培養 35
二、行為觀察 35
三、心跳數值 35
四、解剖 36
伍、實驗流程 36
一、實驗前置作業 36
二、預後評估實驗 37
三、石膏實驗 38
四、白虎湯實驗 38
陸、參數之測量與分析 38
一、血壓與心跳之測量 38
二、血液樣本處理 39
三、細胞激素分析 39
柒、統計方法 40
一、預後評估 40
二、石膏治療 40
三、白虎湯治療 40
第四章　結果 41
壹、預後評估實驗 41
一、基本資料 41
二、不同心跳倍率下死亡組與存活組之介白素6濃度曲線 42
三、不同心跳倍率下死亡組與存活組之介白素10濃度曲線 43
四、不同心跳倍率下死亡組與存活組之介白素6以及介白素
10濃度散佈曲線 44
五、不同心跳倍率下之預後鑑別方程式 47
貳、石膏治療實驗 49
一、3天存活曲線 49
二、各組之血壓與心跳速率比較 49
三、各組之介白素6以及介白素10濃度比較 51
參、白虎湯治療實驗 52
一、各組之血壓與心跳速率比較 52
二、各組之介白素6以及介白素10濃度比較 54
第五章　討論 56
第六章　結論 62
參考文獻 63
附錄 76
英文摘要 80
謝辭 83

1.Wenzel RP and Edmond MB. The impact of hospital-acquired bloodstream infections. Emerg Infect Dis. 2001; 7(2): 174-177.
2.Center for Disease Control.Increase in National Hospital Discharge Survey rates for septicemia--United States, 1979-1987. MMWR Morb Mortal Wkly Rep. 1990; 39(2): 31-34.
3.Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7): 1303-1310.
4.Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time? Crit Care Med. 1998; 26(12): 2078-2086.
5.行政院衛生署十大死因統計，93年。
6.Vincent JL, Sun Q, Dubois MJ. Clinical trials of immunomodulatory therapies in severe sepsis and septic shock. Clin Infect Dis. 2002; 34(8): 1084-1093.
7.Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001; 344(10): 699-709.
8.Annane D, bille V, Charpentier C, Bollaert PE, ois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche? G, Chaumet-Riffaut P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002; 288(7): 862-871.
9.Van Den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001; 345(19): 1359-1367.
10.Opal SM. Clinical trial design and outcomes in patients with severe sepsis. Shock. 2003; 20(4): 295-302.
11.Thomas L. Germs. N Engl J Med. 1972; 287(11): 553-555.
12.Bone RC, Fisher J, Clemmer TP. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987; 317(11): 653-658.
13.Ziegler EJ, Fisher J, Sprung CL, Straube RC, Sadoff JC, Foulke GE, Wortel CH, Fink MP, Dellinger RP, Teng NNH, Allen IE, Berger HJ, Knatterud GL, LoBuglio AF, Smith CR, Kett DH, Elser B, Chan JC, Kelly G. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1991; 324(7): 429-436.
14.Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, Pennington JE, Wherry JC. Efficacy and safety of monoclonal antibody to human tumor necrosis factor α in patients with sepsis syndrome: A randomized, controlled, double-blind, multicenter clinical trial. JAMA. 1995; 273(12): 934-941.
15.Fisher J, Slotman GJ, Opal SM, Pribble JP, Bone RC, Emmanuel G, Ng D, Bloedow DC, Catalano MA. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. The IL-1RA Sepsis Syndrome Study Group. Crit Care Med. 1994; 22(1): 12-21.
16.Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: A reassessment. Crit Care Med. 1997; 25(7): 1095-1100.
17.Natanson C, Suffredini AF, Eichacker PQ, Danner RL. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med. 1994; 120(9): 771-783.
18.Nelson S. A question of balance: Editorial. Am J Respir Crit Care Med. 1999; 159(5 I): 1365-1367.
19.Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996; 24(7): 1125-1126.
20.Kong CW, Tsai K, Chin JH, Chan WL, Hong CY. Magnolol attenuates peroxidative damage and improves survival of rats with sepsis. Shock. 2000; 13(1): 24-28.
21.Huang Y, Wong CM, Lau CW, Yao X, Tsang SY, Su YL, Chen ZY. Inhibition of nitric oxide/cyclic GMP-mediated relaxation by purified flavonoids, baicalin and baicalein, in rat aortic rings. Biochem Pharmacol. 2004; 67(4): 787-794.
22.Chen YC, Shen SC, Chen LG, Lee TJF, Yang LL. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem Pharmacol. 2001; 61(11): 1417-1427.
23.Lee YM, Hsiao G, Chang JW, Sheu JR, Yen MH. Scoparone inhibits tissue factor expression in lipopolysaccharide-activated human umbilical vein endothelial cells. J Biomed Sci. 2003; 10(5): 518-525.
24.Majno G. The ancient riddle of sepsis. J Infect Dis. 1991; 163(5): 937-945.
25.Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RMH, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992; 101(6): 1644-1655.
26.Vincent JL. Dear SIRS, I''m sorry to say that I don''t like you. Crit Care Med. 1997; 25(2): 372-374.
27.Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Chanoin MH, Wolff M, Spencer RC, Hemmer M. The prevalence of nosocomial infection in intensive care units in Europe: Results of the European Prevalence of Infection in Intensive Care (EPIC) study. JAMA. 1995; 274(8): 639-644.
28.Bochud PY, Glauser MP, Calandra T. Antibiotics in sepsis. Intensive Care Med. 2001; 27(7): S33-48.
29.Raetz CRH and Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002; 71: 635-700.
30.Raetz CRH, Ulevitch RJ, Wright SD, Sibley CH, Ding A, Nathan CF. Gram-negative endotoxin: An extraordinary lipid with profound effects on eukaryotic signal transduction. FASEB J. 1991; 5(12): 2652-2660.
31.Jonathan C, William GP. Infectious diseases. Mosby Publishing Co.,Inc., New York 2004; pp. 616.
32.Fenton MJ and Golenbock DT. LPS-binding proteins and receptors. J Leukoc Biol. 1998; 64(1): 25-32.
33.Cohen J. The immunopathogenesis of sepsis. Nature. 2002; 420(6917): 885-891.
34.Ckhed F, Meijer L, Normark S, Richter-Dahlfors A. TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14. Cell Microbiol. 2002; 4(8): 493-501.
35.Michie HR, Manogue KR, Spriggs DR, Revhaug A, O''Dwyer S, Dinarello CA, Cerami A, Wolff SM, Wilmore DW. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988; 318(23): 1481-1486.
36.Cho DR, Shanbhag AS, Hong CY, Baran GR, Goldring SR. The role of adsorbed endotoxin in particle-induced stimulation of cytokine release. J Orthop Res. 2002; 20(4): 704-713.
37.Llewelyn M, Cohen J. Superantigens: Microbial agents that corrupt immunity. Lancet Infect Dis. 2002; 2(3): 156-162.
38.Sriskandan S, Cohen J. The pathogenesis of septic shock. J Infect. 1995; 30(3): 201-206.
39.Jonathan C, William GP. Infectious diseases. Mosby Publishing Co.,Inc., New York 2004; pp. 617.
40.Lynn WA, Cohen J. Adjunctive therapy for septic shock: A review of experimental approaches. Clin Infect Dis. 1995; 20(1): 143-158.
41.Bone RC. Phospholipids and their inhibitors: A critical evaluation of their role in the treatment of sepsis. Crit Care Med. 1992; 20(6): 884-890.
42.Bone RC. Inhibitors of complement and neutrophils: A critical evaluation of their role in the treatment of sepsis. Crit Care Med. 1992; 20(6): 891-898.
43.Bone RC. Modulators of coagulation: A critical appraisal of their role in sepsis. Arch Intern Med. 1992; 152(7): 1381-1389.
44.Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991; 43(2): 109-142.
45.Jonathan C, William GP. Infectious diseases. Mosby Publishing Co.,Inc., New York 2004; pp. 618.
46.Jonathan C, William GP. Infectious diseases. Mosby Publishing Co.,Inc., New York 2004; pp. 618.
47.Anonymous. Guidelines for the management of severe sepsis and septic shock. The International Sepsis Forum. Intensive Care Med. 2001; 27: S1-134.
48.Hurley JC. Antibiotic-Induced release of endotoxin - A therapeutic paradox. Drug Saf. 1995; 12(3): 183-195.
49.Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345(19): 1368-1377.
50.Lefering R and Neugebauer EAM. Steroid controversy in sepsis and septic shock: A meta-analysis. Crit Care Med. 1995; 23(7): 1294-1303.
51.Cullen DJ, Civetta JM, Briggs BA, Ferrara LC. Therapeutic intervention scoring system: a method for quantitative comparison of patient care. Crit Care Med. 1974; 2(2): 57-60.
52.Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE. APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med. 1981; 9(8): 591-597.
53.Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med. 1985; 13(10): 818-829.
54.Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio CA, Murphy DJ, Lotring T, Damiano A, Harrell J. The APACHE III prognostic system: Risk prediction of hospital mortality for critically III hospitalized adults. Chest. 1991; 100(6): 1619-1636.
55.Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med. 1985; 13(10): 818-829.
56.Le Gall JR, Loirat P, Alperovitch A. A simplified acute physiology score for ICU patients. Crit Care Med. 1984; 12(11): 975-977.
57.Lemeshow S, Teres D, Pastides H. A method for predicting survival and mortality of ICU patients using objectively derived weights. Crit Care Med. 1985; 13(7): 519-525.
58.Lemeshow S, Teres D, Klar J, Avrunin JS, Gehlbach SH, Rapoport J. Mortality Probability Models (MPM II) based on an international cohort of intensive care unit patients. JAMA. 1993; 270(20): 2478-2486.
59.Lemeshow S, Klar J, Teres D, Avrunin JS, Gehlbach SH, Rapoport J, Rue M. Mortality probability models for patients in the intensive care unit for 48 or 72 hours: A prospective, multicenter study. Crit Care Med. 1994; 22(9): 1351-1358.
60.Vincent JL, Moreno R, Takala J, Willatts S, De M, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996; 22(7): 707-710.
61.Vincent JL, De Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study. Crit Care Med. 1998; 26(11): 1793-1800.
62.Antonelli M, Moreno R, Vincent JL, Sprung CL, Mendoc?a A, Passariello M, Riccioni L, Osborn J. Application of SOFA score to trauma patients. Intensive Care Med. 1999; 25(4): 389-394.
63.Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: A reliable descriptor of a complex clinical outcome. Crit Care Med. 1995; 23(10): 1638-1652.
64.Moemen ME. Prognostic categorization in systemic sepsis. Egyptian Journal of Anaesthesia. 2003; 19(2): 183-194.
65.Cook R, Cook D, MMath JT, MMath KAL, Marshall J. Multiple organ dysfunction: Baseline and serial component scores. Critical Care Medicine. 2001; 29(11): 2046-2050.
66.Le Gall JR, Klar J, Lemeshow S, Saulnier F, Alberti C, Artigas A, Teres D. The logistic organ dysfunction system: A new way to assess organ dysfunction in the intensive care unit. JAMA. 1996; 276(10): 802-810.
67.李月彩、李成福、李同憲：中醫外感熱病學對感染性全身炎症反應綜合徵的認識。中國中西醫結合急救雜誌 2002; 9(2): 63-4.
68.蔣超：辨證分型治療全身性炎症反應綜合證療效觀察。中國中西醫結合急救雜誌 2004; 11(4): 245-47.
69.胡森、高飛：中醫藥防治多器官功能障礙綜合症探討。中國中醫急症 2000; 9(3): 113-4.
70.王文健、王軼宇：全身性炎症反應與中西醫結合防治。中國中西醫結合雜誌 2005; 25(1): 68-70.
71.孟澍江：溫病學，知音出版社，台北 1991;4: pp. 56.
72.陳揚榮、陳曉玲、鄭旭：溫病氣分證應注重清熱養陰與活血化瘀。福建中醫學院學報 1999; 9(3): 8-9.
73.艾軍：論溫病氣分證治之熱與鬱。廣西中醫藥 1998; 21(3): 41-3.
74.劉景源、王慶俠：溫病辨治匯講第6講溫熱病辨治-氣分證候。中國臨床醫生 1999; 27(2): 66-9.
75.陳揚榮、陳曉玲、陳錦芳、江明、鄭旭：清氣化瘀養陰湯治療溫病氣分證的實驗研究。福建中醫學院學報 1998; 8(4): 23-7.
76.周寧：略論溫病氣分證治。中醫文獻雜誌 1999; 3: 10-1.
77.朱平：論治療溫病營血分證應重視疏利氣機。成都中醫藥大學學報 2001; 24(4): 14-6.
78.胡森、高飛：中醫藥防治多器官功能障礙綜合症探討。中國中醫急症 2000; 9(3): 113-4.
79.胡森、高飛：中醫藥防治多器官功能障礙綜合症回顧與展望。中國中西醫結合急救雜誌 2001; 8(6): 323-5.
80.唐•王冰：素問王冰注，台灣中華，台北 1987; pp. 221.
81.陳玉英：溫病營血分症的病理及治法研究概況。江西中醫藥 2001; 32(4): 56-8.
82.清•葉天士：溫熱論，上海科技，上海 1960; pp. 6.
83.周永學：論衛氣營血辨症的理論依據與臨床意義。陜西中醫函授 1996; 6: 3-5.
84.河北醫學院：靈樞經校釋，人民衛生，北京 1982; pp. 266.
85.河北醫學院：靈樞經校釋，人民衛生，北京 1982; pp. 499.
86.清•葉天士：溫熱論，上海科技，上海 1960; pp. 20.
87.清•葉天士：溫熱論，上海科技，上海 1960; pp. 19.
88.唐由君：中醫治療敗血症近況。山東中醫學院學報 1983; 7(2): 58-61.
89.周思憲：對全身性化膿性感染的症治。新中醫 1986; 4: 53-4.
90.邱祥運、陳培城：膿毒敗血症治驗。新中醫 1996; 4: 50.
91.王蕭蓉：中西醫結合治療敗血症150例。實用中醫藥雜誌 2001; 17(5): 28-9.
92.郎繼孝、李松林：趙炳南益氣養陰法治療敗血症探究。遼寧中醫雜誌 1997; 24(12): 541.
93.清•張山雷：瘍科綱要，啟業，台北市 1982; pp 44.
94.崔雲、茅永斌：涼血清熱解毒治療疔瘡走黃35例。浙江中醫學院學報 199 6; 20(8): 21.
95.明•陳實功：外科正宗，遼寧科技，瀋陽 1997; pp 75.
96.尹燕杰、張玉蘭、趙佳輝：中西醫結合治療膿毒敗血症40例。黑龍江醫學 2001; 25(12): 930.
97.清•高秉鈞：瘍科心得集，旋風，台北縣 1976; pp 4.
98.王煒：內陷出自何處。中醫文獻雜誌 1995; 3: 25-6.
99.清•高秉鈞：瘍科心得集，旋風，台北縣 1976; pp 2.
100. 清•祁坤：外科大成，文光，臺北 1979; pp 267.
101. 明•陳實功：外科正宗，人民衛生，北京 1963; pp 73.
102. 唐•王冰：素問王冰注，台灣中華，台北 1987; pp 14.
103. 王左、熊旭東：感染性休克的當今研究與中醫藥治療。中國中醫急症 1996; 5(4): 188-90.
104. 金妙文、周仲瑛、同小林、葛信國、王志英：抗厥注射液治療感染性休克的研究。中國中醫急症 1996; 5(4): 147-9.
105. 王朝暉：內經中厥字源語義辨析。江西中醫學院學報 2004; 16(6): 27-31.
106. 唐•王冰：素問王冰注，台灣中華，台北 1987; pp 64.
107. 唐•王冰：素問王冰注，台灣中華，台北 1987; pp 227.
108. 明•張介賓：類經，人民衛生，北京 1965; pp 481.
109. 金•成無己：注解傷寒論，廣東經濟出版社，廣州 2000; pp 270.
110. 黃啟福：休克與厥脫證現代研究述評。北京中醫藥大學學報 1994; 17(5): 290-5.
111. 毛春燕：感染性休克的中醫辨證論治初探。實用中西醫結合雜誌 1997; 10(16): 1527-8.
112. 清•吳瑭：溫病條辨，人民衛生，北京 1963; pp 30.
113. 清•吳瑭：溫病條辨，人民衛生，北京 1963; pp 65.
114. 張炳立：溫病熱厥證治析要。天津中醫學院學報 2002; 21(4): 15-6.
115. 唐•王冰：素問王冰注，台灣中華，台北 1987; pp 225.
116. 王仲彬：傷寒論熱厥證機理探討。江西中醫藥 1996; 27(6): 370-1.
117. 金•成無己：注解傷寒論，廣東經濟出版社，廣州 2000; pp 269.
118. 朱文鋒：厥脫概念辨析。中國中醫基礎醫學雜誌 1999; 5(1): 17-8.
119. 楊付明：張錫純治療厥脫思想探要。四川中醫 2004; 22(10): 1-2.
120. 陳玉英：厥脫證的中醫治法研究進展。中國中醫藥信息雜誌 2002; 9(8): 70-1.
121. 民國•中醫編輯學會：溫病學釋義，文光出版社，台北 1981; pp 70-8.
122. 清•吳瑭：溫病條辨，人民衛生，北京 1963; pp 20.
123. 顏正華：中藥學，知音出版社，台北 1998; pp. 115-9.
124. 蕭培根、陰健、郭力弓：中藥現代研究及臨床應用，學苑出版社，北京 1986; pp. 213-6.
125. 顏正華：中藥學，知音出版社，台北 1998; pp. 119-21.
126. 蕭培根、陰健、郭力弓：中藥現代研究及臨床應用，學苑出版社，北京 1986; pp. 444-6.
127. 顏正華：中藥學，知音出版社，台北 1998; pp. 759-67.
128. 蕭培根、陰健、郭力弓：中藥現代研究及臨床應用，學苑出版社，北京 1986; pp. 196-212.
129. Fink MP and Heard SO. Laboratory models of sepsis and septic shock. J Surg Res. 1990; 49(2): 186-196.
130. Parker MM and Parrillo JE. Septic shock Hemodynamics and pathogenesis. JAMA. 1983; 250(24): 3324-3327.
131. D''Orio V, Wahlen C, Rodriguez LM. A comparison of Escherichia coli endotoxin single bolus injection with low-dose endotoxin infusion on pulmonary and systemic vascular changes. Circulatory Shock. 1987; 21(3): 207-216.
132. Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock: A review of laboratory models and a proposal. J Surg Res. 1980; 29(2): 189-201.
133. 民國•張賢哲、蔡貴花：中藥炮製學，中國醫藥學院，台中　1991; pp. 595-6.
134. 民國•張賢哲、蔡貴花：中藥炮製學，中國醫藥學院，台中　1991; pp.244-6.
135. 民國•張賢哲、蔡貴花：中藥炮製學，中國醫藥學院，台中　1991; pp.121-4.
136. Walley KR, Lukacs NW, Standiford TJ, Strieter RM, Kunkel SL. Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infection and Immunity. 1996; 64(11): 4733-4738.
137. Sullivan JS, Kilpatrick L, Costarino J, Lee SC, Harris MC. Correlation of plasma cytokine elevations with mortality rate in children with sepsis. J Pediatr. 1992; 120(4 I): 510-515.
138. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993; 119(8): 771-778.
139. Van Der Poll T, Waal Malefyt R, Coyle SM, Lowry SF. Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: Sequential measurements of plasma soluble interleukin (IL)-1 receptor type II, IL-10, and IL-13. J Infect Dis. 1997; 175(1): 118-122.
140. Rongione AJ, Kusske AM, Ashley SW, Reber HA, McFadden DW. Interleukin-10 prevents early cytokine release in severe intraabdominal infection and sepsis. J Surg Res. 1997; 70(2): 107-112.
141. Doughty L, Carcillo JA, Kaplan S, Janosky J. The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric sepsis-induced multiple organ failure. Chest. 1998; 113(6): 1625-1631.
142. Hack CE, De Groot ER, Felt-Bersma RJF, Nuijens JH, Strack Van Schijndel RJM, Eerenberg-Belmer AJM, Thijs LG, Aarden LA. Increased plasma levels of interleukin-6 in sepsis. Blood. 1989; 74(5): 1704-1710.
143. Calandra T, Gerain J, Heumann D, Baumgartner JD, Glauser MP. High circulating levels of interleukin-6 in patients with septic shock: Evolution during sepsis, prognostic value, and interplay with other cytokines. Am J Med. 1991; 91(1): 23-29.
144. Patel RT, Deen KI, Youngs D, Warwick J, Keighley MRB. Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis. Br J Surg. 1994; 81(9): 1306-1308.
145. Remick DG, Bolgos GR, Siddiqui J, Shin J, Nemzek JA. Six at six: Interleukin-6 measured 6 H after the initiation of sepsis predicts mortality over 3 days. Shock. 2002; 17(6): 463-467.
146. Parsons PE. Interleukin-10: The ambiguity in sepsis continues. Crit Care Med. 1998; 26(5): 818-819.
147. Howard M, Muchamuel T, Andrade S, Menon S. Interleukin 10 protects mice from lethal endotoxemia. J Exp Med. 1993; 177(4): 1205-1208.
148. Rongione AJ, Kusske AM, Kwan K, Ashley SW, Reber HA, McFadden DW. Interleukin-10 Protects Against Lethality of Intra-Abdominal Infection and Sepsis. J Gastrointest Surg. 2000; 4(1): 70-76.
149. Song GY, Chung CS, Chaudry IH, Ayala A. What is the role of interleukin 10 in polymicrobial sepsis: Anti- inflammatory agent or immunosuppressant? Surgery. 1999; 126(2): 378-383.
150. Kahlke V, Dohm C, Mees T, tzmann K, Schreiber S, der J. Early interleukin-10 treatment improves survival and enhances immune function only in males after hemorrhage and subsequent sepsis. Shock. 2002; 18(1): 24-28.
151. Van Dissel JT, Van Langevelde P, Westendorp RGJ, Kwappenberg K, lich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet. 1998; 351(9107): 950-953.
152. Taniguchi T, Koido Y, Aiboshi J, Yamashita T, Suzaki S, Kurokawa A. Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med. 1999; 27(7): 1262-1264.
153. Bosscha K, Reijnders K, Hulstaert PF, Algra A, Van Der Werken C. Prognostic scoring systems to predict outcome in peritonitis and intraabdominal sepsis. Br J Surg. 1997; 84(11): 1532-1534.