【作者】 刘欣瑜；

【导师】 陈星；

【作者基本信息】 中南大学 ， 内科学， 2008， 硕士

【摘要】 目的:通过比较几种吸附剂对肝衰竭患者血浆总胆红素、胆汁酸及血氨的吸附作用,为研究一种新的用于治疗肝衰竭的吸附材料提供帮助。方法:收集四名肝衰竭患者血浆,将每位患者血浆分为十一份,分别使用以下十种吸附材料及空白对照管进行血浆灌流:Ⅰ组为丽珠HA330大孔吸附树脂;Ⅱ组为活性炭+人血白蛋白包被;Ⅲ组为AB-8大孔吸附树脂;Ⅳ组为AB-8大孔吸附树脂+化学处理+人血白蛋白包被;Ⅴ组为AB-12大孔吸附树脂;Ⅵ组为AB-12大孔吸附树脂+化学处理+人血白蛋白包被;Ⅶ组为乙基纤维素+人血白蛋白包被;Ⅷ组为乙基纤维素+化学处理+人血白蛋白包被;Ⅸ组为乙基纤维素+化学处理+多粘菌素E+人血白蛋白包被;Ⅹ组为乙基纤维素+化学处理+丁胺卡那+人血白蛋白包被;Ⅺ组为空白对照组。每组灌流器分别用肝衰竭患者离体血浆灌流,从灌流循环0次(C0),1次(C1),2次(C2),3次(C3)分别留取血浆5ml,检测总胆红素、胆汁酸和血氨的浓度。结果:1.对总胆红素的吸附效果:随着灌流次数的增加,各组血浆内总胆红素浓度均逐渐下降。其中Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组、Ⅷ组、Ⅸ组、Ⅹ组灌流结束时,总胆红素浓度较灌流前明显降低,C3与C0比较,有显著性差异,P＜0.05;Ⅴ组、Ⅵ组、Ⅶ组、Ⅺ组灌流结束后,血浆总胆红素浓度C3较灌流前C0无显著性差异,P＞0.05。各组对总胆红素吸附率比较:Ⅷ组＞Ⅰ组＞Ⅱ组＞Ⅹ组＞Ⅸ组＞Ⅳ组＞Ⅲ组＞Ⅵ＞Ⅶ组＞Ⅴ组＞Ⅺ组,其中Ⅱ组、Ⅹ组组间比较无显著性差异(P＞0.05);Ⅲ组、Ⅳ组、Ⅸ组组间比较无显著性差异(P＞0.05);Ⅴ组、Ⅵ组、Ⅶ组、Ⅸ组组间比较无显著性差异(P＞0.05);其余各组间相互比较均存在显著性差异(P＜0.05)。对总胆红素吸附效果最好的三种材料为Ⅷ组、Ⅰ组、Ⅱ组,其中Ⅷ组最好;而Ⅴ组、Ⅵ组、Ⅶ组对胆红素吸附作用最差。2.对胆汁酸吸附效果:随着灌流次数的增加,各组血浆内胆汁酸浓度均逐渐下降。其中Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组、Ⅴ组、Ⅵ组、Ⅷ组、Ⅸ组、Ⅹ组灌流结束时,胆汁酸浓度较灌流前明显降低,C3与C0比较,有显著性差异,P＜0.05;Ⅶ组、Ⅺ组灌流结束后,血浆总胆汁酸浓度C3较灌流前胆汁酸浓度C0无显著性差异,P＞0.05。各组对胆汁酸吸附率比较:Ⅱ组＞Ⅳ组＞Ⅸ组＞Ⅷ组＞Ⅰ组＞Ⅹ组＞Ⅵ组＞Ⅲ组＞Ⅴ组＞Ⅺ组＞Ⅶ组。其中Ⅳ组、Ⅷ组、Ⅸ组组间比较无显著性差异(P＞0.05);Ⅰ组、Ⅵ组、Ⅹ组组间比较无显著性差异(P＞0.05);Ⅲ组、Ⅴ组组间比较无显著性差异(P＞0.05);Ⅶ组、Ⅺ组组间比较无显著性差异(P＞0.05);其余各组间相互比较均存在显著性差异(P＜0.05)。对胆汁酸吸附效果最好的三种材料为Ⅱ组、Ⅳ组、Ⅸ组、Ⅷ组,其中Ⅱ组最好;而Ⅲ组、Ⅴ组、Ⅷ组对胆红素吸附作用最差。3.对血氨吸附效果:随着灌流次数的增加,各组血浆内血氨浓度均逐渐下降。所有十组吸附剂以及空白对照组灌流结束时,血氨浓度较灌流前明显降低,C3与C0比较,有显著性差异,P＜0.05。各组对血氨吸附率比较:Ⅷ组＞Ⅰ组＞Ⅱ组＞Ⅶ组＞Ⅸ组＞Ⅳ组＞Ⅹ组＞Ⅲ组＞Ⅺ组＞Ⅵ组＞Ⅴ组。其中Ⅳ组、Ⅶ组、Ⅸ组、Ⅹ组组间比较无显著性差异(P＞0.05);Ⅴ组、Ⅵ组、Ⅺ组组间比较无显著性差异(P＞0.05)。其余各组间相互比较均存在显著性差异(P＜0.05)。对血氨吸附效果最好的三种材料为Ⅷ组、Ⅰ组、Ⅱ组,其中Ⅷ组最好;而Ⅴ组、Ⅵ组对血氨吸附作用最差。结论:1.对总胆红素的吸附力由强到弱依次为:乙基纤维素(化学处理+人血白蛋白包被)＞丽珠HA330大孔树脂＞活性炭(人血白蛋白包被)、乙基纤维素(化学处理+丁胺卡那+人血白蛋白包被)＞乙基纤维素(化学处理+多粘菌素E+人血白蛋白包被)、AB-8大孔吸附树脂(化学处理+人血白蛋白包被)、AB-8大孔吸附树脂。而AB-12大孔吸附树脂、AB-12大孔吸附树脂(化学处理+人血白蛋白包被)、乙基纤维素(人血白蛋白包被)对总胆红素没有吸附作用。2.对胆汁酸的吸附力由强到弱依次为:活性炭(人血白蛋白包被)＞AB-8大孔吸附树脂(化学处理+人血白蛋白包被)、乙基纤维素(化学处理+人血白蛋白包被)、乙基纤维素(化学处理+多粘菌素E+人血白蛋白包被)＞丽珠HA330大孔树脂、AB-12大孔吸附树脂(化学处理+人血白蛋白包被)、乙基纤维素(化学处理+丁胺卡那+人血白蛋白包被)＞AB-8大孔吸附树脂、AB-12大孔吸附树脂。而经人血白蛋白包被的乙基纤维素对胆汁酸没有吸附作用。3.对血氨的吸附力由强到弱依次为:乙基纤维素(化学处理+人血白蛋白包被)＞丽珠HA330大孔树脂＞活性炭(人血白蛋白包被)＞AB-8大孔吸附树脂(化学处理+人血白蛋白包被)、乙基纤维素(人血白蛋白包被)、乙基纤维素(化学处理+多粘菌素E+人血白蛋白包被)、乙基纤维素(化学处理+丁胺卡那+人血白蛋白包被)＞AB-8大孔吸附树脂。而AB-12大孔吸附树脂和经化学处理及蛋白包被的AB-12大孔吸附树脂对血氨均没有吸附作用综合上述结论,对总胆红素、胆汁酸、血氨的吸附作用最好的三种吸附剂依次为:乙基纤维素+化学处理+人血白蛋白包被、丽珠HA330大孔树脂、活性炭+人血白蛋白包被。更多还原

【Abstract】 Objective:Compared the clearance effect of plasma perfusion on Hepatic failure patient by several sorbents,to make some helps for the development of a new clinical effective hemoperfusion sorbent to treat the hepatic failure.Methods:Collect four hepatic failure patients’ plasma sample,and assigned each plasma into 11 groups according to different sorbents:GroupⅠ:synthesis macroporous adsorptive resin of single use hemoperfutor from LIVZON corporation;groupⅡ:activated charcoal coating with albumin; groupⅢ:AB-8 macroporous adsorptive resin;groupⅣ:AB-8 macroporous adsorptive resin with diamine arms and coating with albumin;groupⅤ:AB-12 macroporous adsorptive resin;groupⅥ:AB-12 macroporous adsorptive resin with diamine arms and coating with albumin;groupⅦ:ethyl cellulose coating with albumin;groupⅧ:ethyl cellulose with glutaraldehyde arms and coating with albuminGroupⅨ:ethyl cellulose with PME ligands and coating with albumin;groupⅩ:ethyl cellulose with AMIKACINI ligands and coating with albumin;groupⅪ:blank.The hepatic failure patients’ plasma was treated by the 11 hemoperfutor individually.And plasma total bilirubin（TBIL）,bile acid（TBA）,blood ammonia（NH₃）were detected before perfusion（CO）,and after the first（C1）, second（C2）,third（C3）cycle.Result:1.The clearance effect on total bilirubin:Following the process of plasma perfusion,the concentration of TBIL of groupⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅷ,Ⅸ,Ⅹwas lower and lower.There was significant difference between C3 and C0 of each group,（p＜0.05）.But in groupⅤ,Ⅵ,ⅪandⅦ,the concentration after plasma perfusion was almost the same as the initial concentration,no significant difference between C3 and C0 of each group（p＞0.05）.And the result of contrasting clearance effect on TBIL of sorbents was: groupⅧ＞groupⅠ＞groupⅡ＞groupⅩ＞groupⅨ＞groupⅣ＞groupⅢ＞groupⅥ＞groupⅦ＞groupⅤ＞groupⅪ.There was no significant difference between groupⅡand groupⅩ（p＞0.05）,also no significant difference among groupⅢ,groupⅣand groupⅨ（p＞0.05）,and no significant difference among groupⅥ,groupⅦ,groupⅤand groupⅪ.But significant difference was existed between each two others（p＜0.05）.The groupⅧhad the best clearance effect on TBIL.On the contrary,the groupⅥ,groupⅦ,groupⅤand groupⅪhad the worst clearance effect. 2.The clearance effect on TBA:Following the process of plasma perfusion,the concentration of TBA of groupⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,Ⅵ,Ⅷ,Ⅸ,Ⅹwas lower and lower.There was significant difference between C3 and C0 of each group, （p＜0.05）.But in groupⅪandⅦ,the concentration after plasma perfusion was almost the same as the initial concentration,no significant difference between C3 and C0 of each group（p＞0.05）.And the result of contrasting clearance effect on TBA of sorbents was: groupⅡ＞groupⅣ＞groupⅨ＞groupⅧ＞groupⅠ＞groupⅩ＞groupⅥ＞groupⅢ＞groupⅤ＞groupⅪ＞groupⅦ.There was no significant difference between groupⅣ,groupⅨand groupⅧ,（p＞0.05）,no significant difference among groupⅠ,groupⅩ,groupⅥ,（p＞0.05）,also no significant difference among groupⅢand groupⅤ,and no significant difference among groupⅪand groupⅦ.But significant difference was existed between each two others（p＜0.05）.The groupⅡhad the best clearance effect on TBA.On the contrary,the groupⅢ,groupⅦ,groupⅤand groupⅪhad the worst clearance effect. 3.The clearance effect on blood ammonia:Following the process of plasma perfusion,the concentration of NH₃ of all groups was lower and lower,There was significant difference between C3 and C0 of each group,（p＜0.05）.And the result of contrasting clearance effect on NH₃ of sorbents was groupⅧ＞groupⅠ＞groupⅡ＞groupⅦ＞groupⅨ＞groupⅣ＞groupⅩ＞groupⅢ＞groupⅪ＞groupⅥ＞groupⅤ.There was no significant difference between groupⅣ,groupⅦ,groupⅩand groupⅨ（p＞0.05）, and also no significant difference among groupⅤ,groupⅥand groupⅪ. But significant difference was existed between each two others（p＜0.05）.The groupⅧhad the best clearance effect on NH₃.On the contrary,the groupⅥ,groupⅤand groupⅪhad the worst clearance effect. Conclusion:1.Clearance effect on bilirubin of sorbents was:ethyl cellulose with glutaraldehyde arms and coating with albumin＞synthesis macroporous adsorptive resin of single use hemoperfutor from LIVZON corporation.＞activated charcoal coating with albumin,ethyl cellulose with AMIKACINI ligands and coating with albumin＞ethyl cellulose with PME ligands and coating with albumin,AB-8 macroporous adsorptive resin,AB-8 macroporous adsorptive resin with diamine arms and coating with albumin.And AB-12 macroporous adsorptive resin,AB-12 macroporous adsorptive resin with diamine arms and coating with albumin and ethyl cellulose coating with albumin can not remove bilirubin.2.Clearance effect on bile acid of sorbents was:activated charcoal coating with albumin＞AB-8 macroporous adsorptive resin with diamine arms and coating with albumin,ethyl cellulose with glutaraldehyde arms and coating with albumin,ethyl cellulose with PME ligands and coating with albumin＞synthesis macroporous adsorptive resin of single use hemopeffutor from LIVZON corporation,AB-12 macroporous adsorptive resin with diamine arms and coating with albumin,ethyl cellulose with AMIKACINI ligands and coating with albumin＞AB-12 macroporous adsorptive resin,AB-8 macroporous adsorptive resin.And ethyl cellulose coating with albumin can not remove bile acid. 3.Clearance effect on bl0od ammonia of sorbents was:ethyl cellulose with glutaraldehyde arms and coating with albumin＞synthesis macroporous adsorptive resin of single use hemoperfutor from LIVZON corporation＞activated charcoal coating with albumin＞AB-8 macropomus adsorptive resin with diamine arms and coating with albumin,ethyl cellulose coating with albumin,ethyl cellulose with PME ligands and coating with albumin,ethyl cellulose with AMIKACINI ligands and coating with albumin＞AB-8 macroporous adsorptive resin.And AB-12 macropomus adsorptive resin with diamine arms and coating with albumin,AB-12 macroporous adsorptive resin can not remove blood ammonia.In summary,ethyl cellulose with glutaraldehyde arms and coating with albumin,synthesis macroporous adsorptive resin of single use hemoperfutor from LIVZON corporation and activated charcoal coating with albumin,are the most effective sorbents for bilirubin,bile acid and blood ammonia.And the ethyl cellulose with glutaraldehyde arms and coating with albumin have large application potential.更多还原