Abstract
本研究以 pyridoxal 5'-phosphate(PLP) 修飾血紅素，再以glutaraldehyde(GLUT)為交聯劑進行反應得到的聚合血紅素(PP Hb)為對象。第一部份探討 GLUT/Hb 莫耳比、聚合反應時間及血紅素起始濃度對分子量分佈的影響，並分析反應過程中鐵血紅素 (Met Hb)的生成。結果顯示聚合反應之反應速率非常快速， 反應時間對分子量的影響不大，兩小時可以達到 63%之聚合度。起始血紅素濃度 10-16.12 g/dL時，可以得到 63% - 68% 的聚合量，隨著濃度增高，聚合度會增高。 GLUT/Hb 莫耳比是決定聚合度最重要的因素，GLUT/Hb=7/1或 8/1時所獲得的分子量分佈較為平均； 9/1 和 10/1的比例使得未聚合比例大幅下降，大分子量的比例相對提高。第二部份探討聚合型血紅素的流變特性。 溫度對聚合血紅素的影響符合 Andrade and Arrhenius 關係式。本研究整合了分子量以及血紅素濃度對黏度的影響於 K值及 Ea值中；定義一特殊黏度值，推導了一個實驗式來描述聚合血紅素黏度為一溫度、血紅素濃度及重量平均分子量的函數：μspc=5.505E-8*MW^1.23234*exp(Eao(1.24558-0.01625C)/RT+0.18045C)以這個實驗式來預測聚合血紅素的黏度，預測值與實驗值可以得到 R=0.97的高度相關性。剪切速率對聚合血紅素黏度的影響，在 15-450 sec-1範圍時，黏度幾乎呈一定值，屬於牛頓流體；在小於15sec-1時， 黏度的增加顯示有凝聚現象產生。模擬聚合血紅素輸入人體之情形，將聚合血紅素和Hct45% 之人血球懸浮液相混合，以對數關係式計算混合後之黏度變化，誤差在 10% 左右。最後，以聚合血紅素進行血液稀釋之動物實驗，結果顯示能有效增加十三個區域的腦血流。聚合血紅素黏度低、近乎牛頓流體及攜氧特性使其具有替代 Geloplasma 之優勢。This study is composed of three parts. First, to investigatethe effects of reaction time, GLUT/Hb and initial hemoglobinconcentration on the polymerization degree(PD) in theproduction of Pyridoxylated Poly-Hemoglobin(PP Hb). The resultsshow that the polymerization can reach to 63% polymerization in2 hours. Initial hemoglobin concentration ranging from 10 to16.12 g/dL will produce properly polymerization of 63% to 68%.The GLUT/Hb molar ratio is the most important factor to decidethe PD. With the GLUT/Hb of 7/1 and 8/1,there is only slightdifference in MW distribution. The high MW percentage increasesas unpolymerized part decreases when GLUT/Hb molar ratio is at9/1 and 10/1. The second part is to investigate the rheologicalproperties of PP Hb. The temperature effect on viscosity of PPHb fits the Andrade and Arrhenius Equation. We integrate theinfluence of hemoglobin concentration and weight-average MW(MWw) into K value and Ea value. We arrive at an empiricalequation:μspc=5.505E-8*MW^1.23234*exp(Eao(1.24558-0.01625C)/RT+0.18045C) The predicted viscosities of PP Hb and thoseexperimental values have a very good correlation with R=0.97.The shear dependence of viscosity of PP Hb indicates the flowbehavior of PPHb close to the Newtonian fluid. Animalexperiment is the third part. Hemodilution with PP Hb canincrease the LCBF(local cerebral blood flow).In other case ofhemodilution with carotid-ligated rats,it can also improve theLCBF in most parts of the brain structures.