- 學位論文
一、葡萄製品成分「異戊胺」藉由抑制發炎反應及減少一氧化氮產生來改善菌血性休克小鼠存活率及早期凝血障礙的機制探討。 二、在台灣正常人口中 Schober檢驗的人體測量。
一、Novel function of isoamylamine in grape products: Suppresses inflammation and nitric oxide production, and improves survival in endotoxemic mice by ameliorating coagulopathy at early stage. 二、The anthropometric measurement of Schober’s test in normal Taiwanese population.
摘要
一、葡萄製品成分「異戊胺」藉由抑制發炎反應及減少一氧化氮產生來改善菌血性休克小鼠存活率及早期凝血障礙的機制探討。 當病人罹患內毒素休克 (endotoxemic shock)或敗血性休克 (septic shock, SS)時，會導致許多症狀，其中包括彌漫性血管內凝血（disseminated intravascular coagulation , DIC）現象。敗血性休克（SS）會引起凝血時間 (coagulation time)先縮短，然後逐漸增長，最終變得延長並引發DIC。異戊胺（isoamylamine, IA）是葡萄製品的主要成分之一，經過我們實驗可以改善內毒素 (endotoxin)-脂多醣體（lipopolysaccharide, LPS）誘導內毒素性休克的存活率。這項研究的目的著重在闡明IA改善LPS誘導早期的凝血病變。我們研究了IA對凝固系統的外在途徑-凝血酶原時間（prothrombin time, PT）和內在途徑-部分凝血活酶時間（activated partial thromboplastin time, aPTT）的影響；在LPS腹腔內注射 1mL的1,000 ppm IA給藥後，接著從小鼠抽取的血漿中進行 PT與 aPTT測試。在施予 LPS後1小時後，1,000 ppm IA可以改善 PT縮短的現象，但對 aPTT不具影響；也就是 1,000 ppm IA具部分中介LPS誘導的早期損傷，在小鼠被 LPS處理後1小時，能改善血漿中 PT縮短之影響。此外，我們發現 1,000 ppm IA在小鼠肝細胞萃取物中，係可以透過的 p-ERK / p-p38信號路徑來減弱 MMP-9蛋白的表現量。本項研究主要著重在 IA對血液凝固功能和發炎蛋白的影響。在當前缺乏 SS有效治療的情況下，IA能夠提高存活率並且提供避免在內毒素性休克期間，導致患者死亡的另一選擇。 在 IA對凝血功能的影響，以不同時間處理研究 (time course study)及不同劑量研究 (dose response study)來實驗。在時間處理部分，小鼠於 1000 ppm IA注射後1小時，aPTT即出現延長特性，而 PT則需在2小時後才延長；在劑量處理部分，小鼠於注射後3小時，1 ppm IA 即可使 aPTT產生顯著延長特性，而 PT延長則需 1,000 ppm IA處理才出現延長。小鼠經注射1,000 ppm IA後，產生有aPTT 延長 22.0％（p值 <0.001）、血小板數目被抑制 25.9％（p = 0.039）及 NO產生受抑制 22.3％（p = 0.013）等特徵，也就是一氧化氮抑制似乎與血小板抑制相關，而這現象又與 aPTT延長相關。我們的研究結果顯示腹腔注射IA後，小鼠凝血系統包括內在和外在途徑遭受到抑制，於注射後三小時，IA更能顯著降低血液中的白血球與血小板計數、以及降低血漿中的NO生成。 二、在台灣正常人口中 Schober檢驗的人體測量。 對於評估包括僵直性脊椎炎(ankylosing spondylitis，簡稱AS)在內的下背痛(lower back pain)，有必要測量下背部活動性。在日常免疫風濕科與骨科門診，原始的Schober測試 （original Schober’s test, OST）及修改的Schober測試（modified Schober’s test, MST）普遍被用來測量下背的活動性。據我們所知，本論文報告是東方正常人群中唯一的人體測量參考研究。從年齡最小（20-30歲）到年齡最大（70-80歲）的正常人群體，男性受試者之 OST隨年齡增長從5.0 cm下降至3.1 cm，女性受試者則從3.6 cm降至2.4 cm。使用統計學比對分析，在任一年齡層男性 OST數據都比女性 OST高，p值在 0.009~0.001之間(71~80歲之群除外)。在三個年齡組別中的每一個群組，不論男女性別之OST和MST，都有良好的相關性。
並列摘要
一、Novel function of isoamylamine in grape products: Suppresses inflammation and nitric oxide production, and improves survival in endotoxemic mice by ameliorating coagulopathy at early stage. When a host suffers from endotoxemic shock or septic shock, it results in many symptoms including disseminated intravascular coagulation (DIC). Septic shock (SS) causes coagulation time to decrease and then gradually increase, finally becoming prolonged and giving rise to DIC. Isoamylamine (IA) is one of the main components of grape products and can improve the survival rate of endotoxin lipopolysaccharide (LPS)-induced endotoxemic shock. The aim of this study was to elucidate if IA ameliorates coagulopathy in the early phase of LPS-induced damage. We studied the effects of IA on the coagulation system of extrinsic (prothrombin time, PT) and intrinsic (activated partial thromboplastin time, aPTT) pathways. PT and aPTT were tested in plasma drawn from mice following intraperitoneal (IP) injection of 1 mL of 1,000 ppm IA after LPS administration. Shortened PT was ameliorated by 1,000 ppm IA one hour after LPS administration, but there was no effect on aPTT. In conclusion, IA 1,000 ppm partially intervenes in the early phase of LPS-induced damage, shortening plasma PT one hour after LPS treatment in mice. Furthermore, we found 1,000 ppm IA also could attenuate MMP-9 expression through p-ERK/p-p38 signaling in mice hepatocyte extracts. This study focused on the effects of IA on blood coagulation function and inflammatory proteins. In the current situation of absence of effective treatment for SS, IA can increase survival rate and may offer another choice of patient avoiding causing death during endotoxemic shock. The effects of IA on coagulation were divided into time course and dose response study. In a time course study on coagulation in mice, injection of IA prolonged aPTT in 1 h and PT in 2 h. In a dose study using mice, aPTT was significantly prolonged at 1 ppm, and PT at 1,000 ppm 3h after injection. Mice injected with 1,000 ppm IA had a 22.0% prolongation of aPTT (p value<0.001), 25.9% suppression of platelet counts (p=0.039), and 22.3% suppression of NO production (p=0.013). NO suppression was seemingly related to platelet suppression, which in turn was related to aPTT prolongation. Our results showed that intraperitoneal injection of IA suppressed the murine coagulation system including both intrinsic and extrinsic pathways in mice. Three hours after injection, IA significantly decreased WBC and platelet counts in the blood and NO production in plasma. 二、The anthropometric measurement of Schober’s test in normal Taiwanese population. The measurement of lower back mobility is essential in the assessment of lower back pain including ankylosing spondylitis. The original Schober’s test (OST) and modified Schober’s test (MST) are popularly conducted in daily rheumatology and orthopedics clinical practices. To our knowledge, this report is the only anthropometric reference study in a normal oriental population. The OST declined with age from 5.0 cm in the youngest (20-30 years old) to 3.1 cm in the aged (70-80 years old) male subjects, and from 3.6 cm to 2.4 cm in the female subjects. The male OST was statistically more than the female OST. There was a good correlation between OST and MST in each of the three age groups of both sexes.
參考文獻
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- 余采臻、歐欣怡、郭雲鼎、陳瑛芳、余漢倫（2021）。【論文摘要】Respiratory Care Experience: Using High-Frequency Oscillatory Ventilation in The Extremely Low-birthweight Infant of Hypercapnic Acidosis Complicated with Pneumothorax and Pulmonary Hypertension。呼吸治療，20(2)，134-135。https://doi.org/10.6269/JRT.202107_20(2).0051
- 呂孟潔、蕭惟珍、郭耀文、吳惠東、陳惠娟（2022）。【論文摘要】Evidence-Based Evaluation: Can Esophageal Pressure -Guided Strategy Improve Survival and Days Free From Mechanical Ventilator In Patients With Acute Respiratory Distress Syndrome。呼吸治療，21(2)，104-105。https://doi.org/10.6269/JRT.202207_21(2).0027
- Lin, L., & Chen, Y. H. (2022). 【論文摘要】Development of Spodoptera frugiperda (Lepidoptera: Noctuidae) on Three Different Artificial Diets and Controlling Effect with Chemical-free Pesticides. 花蓮區農業改良場研究彙報英文摘要版, (), 89-89. https://www.airitilibrary.com/Article/Detail?DocID=P20150127001-N202301050003-00006
- Sung, P. H., Yip, H. K., Wu, C. J., Yang, C. H., Chen, C. J., & Hsueh, S. K. (2019). 【論文摘要】Impact of Distal Protection or Glycoprotein IIb/IIIa Inhibitor Combined with Aspiration Thrombectomy in Primary PCI On Short-term Angiographic and Echocardiographic Results and Long-term Clinical Outcomes. 海峽循環醫學雜誌, 1(2S), 85-85. https://doi.org/10.6907/SCJ.201909/SP_1(2).0071
- Huang, Y. W., Ye, Y. R., Chien, C., Yawichai, W., & Mu, H. Y. T. (2022). 【論文摘要】The Comparison of Intermediate, Short-Term, and Long-Term of Treatment Effects Between Manual Therapy and Supervised Therapeutic Exercise for Patients With Chronic Neck Pain: A Systematic Review and Meta-Analysis. 物理治療, 47(2), 158-159. https://doi.org/10.6215/FJPT.202206.P50