臺灣博碩士論文加值系統

創傷出血性休克患者因血液大量流失，致使全身能量及氧氣缺乏，需盡快止血並給予復甦液。但復甦時會增加體內氧化壓力，導致全身性發炎、多重器官衰竭甚至死亡。研究指出抗氧化的維生素、參與能量代謝的維生素及麩醯胺，可降低氧化壓力、增加能量合成及提供免疫細胞能量。故本實驗欲探討單獨或同時給予大鼠補充麩醯胺及綜合維生素，對創傷出血性休克及復甦(trauma hemorrhagic shock and resuscitation, THR)引發之發炎反應及標的器官損傷的影響。雄性SD大鼠分為六組，除正常對照組及插管假手術組，其餘各組皆進行5公分腹部創傷手術及左頸動脈及右頸靜脈插管(THR大鼠)。由THR大鼠動脈連續抽血10分鐘，使平均動脈壓降為30至35 mmHg。維持低血壓60分鐘後，於10分鐘內輸入抽出的血液及同體積之乳酸林格氏液(LR)或同體積且分別添加L-丙胺-L-麩醯胺酸(L-alanyl-L-glutamine)及綜合維生素或兩者同時給予之LR。SM組與THR大鼠另外給予連續慢速輸注添加或不添加L-丙胺-L-麩醯胺與綜合維生素的LR。大鼠在連續慢速輸注42小時後犧牲。結果顯示，THR大鼠顯著增加血清麩胺丙酮酸轉胺酶濃度，且降低血漿及肺臟間白素(Interleukin，IL)-4濃度。在THR大鼠，單獨給予麩醯胺顯著增加紅血球硫醇基濃度及空腸干擾素(Interferon，IFN)-γ含量，且降低肝臟腫瘤壞死因子(Tumor necrosis factor ，TNF)-a含量；單獨給予綜合維生素顯著增加血漿骨髓過氧化酶(Myeloperoxidase，MPO)活性、肺臟及空腸IL-8含量，且顯著降低血清白蛋白濃度與肺臟IL-10含量；同時給予麩醯胺及綜合維生素顯著增加血清尿素氮濃度及肺臟MPO活性，且降低血清膽固醇濃度及肝臟與腎臟IL-8含量。單獨給予麩醯胺或綜合維生素顯著增加血漿丙二醛濃度及空腸IL-4與IL-6含量；單獨給予麩醯胺或合併給予綜合維生素顯著增加空腸MPO活性，且顯著降低肝臟IL-4濃度及空腸細胞凋亡現象；單獨給予綜合維生素或合併給予麩醯胺顯著增加空腸腺窩深度及肌肉層厚度，且顯著降低紅血球丙二醛濃度及肝臟IL-6含量；單獨或同時給予麩醯胺及綜合維生素顯著降低血漿IFN-γ濃度、肝臟蛋白羰基與IL-10含量及肝臟與腎臟細胞間黏附分子-1含量。綜上所述，給予限量體積的復甦及連續慢速輸注，可改善THR大鼠之血液動力學不穩定，若於復甦液中合併添加麩醯胺及綜合維生素可進一步減緩肝臟的氧化壓力、全身性與腎臟發炎反應及空腸細胞凋亡，進而減少標的器官的損傷。

Hemorrhagic shock patients have huge loss of blood, may lead to energy and oxygen deficit and hypoxia. It shall be given as soon as possible to stop bleeding and fluid resuscitation. However, resuscitation may augment oxidative stress which leads to systemic inflammation, multiple organ failure, and even death. Recent studies indicated that antioxidant vitamins, energy metabolism-associated vitamins, and glutamine may alleviate oxidative stress, elevate energy synthesis, and provide energy for immune cells, respectively. Therefore, the aim of this study was to investigate the effects of single and combined treatment of glutamine and multiple vitamins on inflammatory response and target organ damage in rats with trauma hemorrhagic shock and resuscitation (THR). Male SD rats were divided into 6 groups including a normal control group, an intubation sham-operated group, and 5 groups with 5 cm midline laparotomy and catheterization in the left carotid artery and right jugular vein. The blood was withdrawn from the carotid artery within 10 min until a mean arterial pressure was 30 to 35 mmHg in THR rats. After maintained with low blood pressure for 60 minutes, rats were resuscitated with shed blood and equal volume of lactate Ringer’s solution (LR) without or with L-alanyl-L-glutamine, multiple vitamins or L-alanyl-L-glutamine plus multiple vitamins within 10 min. Sham-operated group and THR rats were infused with continuous, slow rate of LR with or without L-alanyl-L-glutamine and multiple vitamins. Rats were executed after infused with continuous, slow rate of LR solution for 42 hours. The results showed that THR rats significantly increased serum glutamic-pyruvic transaminase and decreased plasma and lung interleukin (IL)-4. In the THR rats, glutamine significantly increased red blood cell sulphydryl group and jejunum interferon (IFN)-γ and decreased liver tumor necrosis factor (TNF)-a. Multiple vitamins significantly increased plasma myeloperoxidase (MPO) activity, lung and jejunum IL-8 and decreased serum albumin and lung IL-10. Glutamine and multiple vitamins significantly increased serum blood urea nitrogen and lung MPO activity and decreased serum cholesterol, liver and kidney IL-8. Glutamine or multiple vitamins significantly increased plasma malondialdehyde, jejunum IL-4 and IL-6. Glutamine with or without multiple vitamins significantly increased jejunum MPO activity and decreased liver IL-4 and jejunum cell apoptosis. Multiple vitamins with or without glutamine significantly increased crypt depth and muscularis thickness and decreased red blood cell malondialdehyde and liver IL-6. Glutamine and/or multiple vitamins significantly decreased plasma IFN- γ, liver protein carbonyl and IL-10, liver and kidney intercellular adhesion molecule. Taken together, limit volume resuscitation and slow rate of infusion may improve hemodynamics unstable in THR rats. Supplementation of glutamine and multiple vitamins in resuscitation solution can alleviate liver oxidative stress, system and kidney inflammation and jejunum apoptosis, further may decrease target organ injury.

中文摘要 I
Abstract III
誌謝 V
目錄 VII
表目錄 XII
圖目錄 XIII
縮寫 XV
第一章 1
緒言 1
第二章 3
文獻回顧 3
一、創傷出血性休克及復甦 3
(一).生理變化 4
(二).水腫 5
(三).凝血障礙 6
(四).多重器官衰竭 7
二、病理機制 10
(一).活性氧物質 10
(二).發炎反應 14
(三).細胞凋亡與增生 19
三、創傷出血性休克之復甦治療 22
(一).復甦液的種類 22
(二).膠體輸液 23
(三).晶體輸液 24
(四).復甦體積 25
(五).復甦方式 26
四、營養添加之復甦液 27
(一).復甦液-胺基酸 27
(二).復甦液-維生素 34
第三章 42
目的與假說 42
第四章 44
方法與材料 44
一、實驗動物與實驗設計 44
(一).實驗動物 44
(二).實驗設計組別說明： 46
(三).實驗流程 47
二、分析方法 48
(一).血液與生化參數 48
(二).血漿中胺基酸的含量 48
(三).局部與全身性發炎反應 50
(四).骨髓過氧化酶的活性 51
(五).非酵素型抗氧化相關因子指標 51
(六).蛋白羰基的含量 54
(七).脂質過氧化物的含量 55
(八).酵素型抗氧化相關因子指標 55
(九).標的器官形態的變化 58
(十).肺臟與空腸水分含量 59
(十一).標的器官的細胞凋亡 59
(十二).標的器官的細胞增生 60
三、統計方法 61
第五章 62
實驗結果 62
一、動物體重及THR模式的誘導 62
二、血球細胞數目 63
三、血清生化值 63
四、血漿中胺基酸含量 67
五、血漿中發炎媒介物 69
六、血漿中抗氧化相關物質 72
七、血漿中氧化相關物質 76
八、紅血球中抗氧化酵素與相關物質 78
九、紅血球中脂質過氧化物 83
十、組織器官的重量與型態 85
十一、組織質量 94
十二、肝臟組織的發炎媒介物及氧化相關物質 97
十三、肝臟細胞的凋亡與增生 101
十四、肺臟組織的發炎媒介物 105
十五、肺臟細胞的凋亡與增生 109
十六、腎臟組織的發炎媒介物 113
十七、腎臟細胞的凋亡與增生 116
十八、空腸組織的發炎媒介物 120
十九、空腸細胞的凋亡與增生 123
第六章 127
討論 127
一、創傷出血性休克及復甦造成的生理變化 127
二、創傷出血性休克及復甦造成的氧化壓力 130
三、創傷出血性休克及復甦造成的發炎反應 131
四、單獨添加麩醯胺對創傷出血性休克及復甦的影響 135
五、單獨添加綜合維生素對創傷出血性休克及復甦的影響 137
六、添加麩醯胺及綜合維生素對創傷出血性休克及復甦的影響 141
七、實驗限制 144
八、總結 144
第七章 146
結論 146
第八章 147
參考文獻 147
附錄 160

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