家蝇抗真菌肽maf-1a大鼠药代动力学初探

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1、贵阳医学院2013届硕士研究生论文《中国图书资料分类法》分类号：R384单位代码：10660学号：S090036贵阳医学院2013届硕士学位论文家蝇抗真菌肽MAF-1A大鼠药代动力学初探研究生：杨华导师：吴建伟教授年级：研2009级专业：病原生物学2013年5月22日贵阳医学院2013届硕士研究生论文1目录摘要„„„„„„„„„„„„„„„„„„„„„„„„2前言„„„„„„„„„„„„„„„„„„„„„„„„4材料与方法„„„„„„„„„„„„„„„„„„„„„„6结果„„„„„„„„„„„„„„„„„„„„„„

2、„„10讨论„„„„„„„„„„„„„„„„„„„„„„„„19参考文献„„„„„„„„„„„„„„„„„„„„„„„23英文摘要„„„„„„„„„„„„„„„„„„„„„„„25致谢„„„„„„„„„„„„„„„„„„„„„„„„27略缩词表„„„„„„„„„„„„„„„„„„„„„„„28论文原创性声明„„„„„„„„„„„„„„„„„„„„29附：综述„„„„„„„„„„„„„„„„„„„„„„302贵阳医学院2013届硕士研究生论文家蝇抗真菌肽MAF-1A大鼠药代动力学初探病原生物学研究生：杨华导师：吴建伟

3、摘要目的：MAF-1A大鼠药代药动力学及影响因素初步研究。方法：1、建立血清MAF-1A高效液相(HPLC)测定法，验证方法稳定性。2、药代动力学分析:Wistar大鼠15只，随机分为三组，每组经尾静脉注射MAF-1A5mg/kg（低剂量组）,10mg/kg（中剂量组）,20mg/kg（高剂量组）。分别于给药后5，10，20，30，60min断尾取血，进行HPLC血清MAF-1A含量分析。用[1]药动学PKSolver软件对数据进行自动拟合处理，药代动力学各项参数计算采用（非房室模型）统计矩参数计算。3、血液中MA

4、F-1A稳定性分析：取大鼠血清，血浆和全血，分别加入1μg/ml（低剂量），5μg/ml（中剂量），25μg/ml（高剂量）MAF-1A混匀，5，10，20，30，60min后经处理样本进行HPLC分析,每个时间点5个质控样本。结果：（1）本实验中MAF-1A的HPLC测量法稳定性好;线性方程为y=0.1999x-0.0107(r=0.9975);高、中、低三种不同浓度样本的精确度<15%，回收率96.59±5.38%，样品稳定性>94%。（2）血清MAF-1A主要药代学参数：低浓度组t1/2=15±2min,MR

5、T=16±2min，Cl=0.16±0.05(μg)/(μg/ml)/min；中浓度组t1/2=15±5min,MRT=15±4min，Cl=0.15±0.05(μg)/(μg/ml)/min。高浓度组t1/2=18±10min,MRT=14±2min，Cl=0.12±0.03(μg)/(μg/ml)/min。三个剂量组的药代学参数无统计学差异（P＞0.05）。（3）MAF-1A血液稳定性：血清稳定性，低浓度组t1/2=26±3min,MRT=37±2min，中浓度组t1/2=48±14min,MRT=68±19m

6、in，高浓度组t1/2=48±7min,MRT=50±10min；血浆低浓度组t1/2=32±贵阳医学院2013届硕士研究生论文35min,MRT=45±6min，中浓度组t1/2=44±5min,MRT=62±9min，高浓度组t1/2=50±16min,MRT=72±17min；全血低浓度组t1/2=59±10min,MRT=86±13min，中浓度组t1/2=50±12min,MRT=73±19min，高浓度组t1/2=50±11min,MRT=78±11min。血清和血浆中不同MAF-1A浓度之间差异，以及

7、低剂量的三种样本之间差异具有统计学意义（P<0.05），中浓度和高浓度三种样本差异，以及全血不同MAF-1A浓度差异不具有统计学意义（P>0.05）。结论：MAF-1A大鼠尾静脉给药后，半衰期15min，影响因素初步分析得血清中蛋白酶可以降解MAF-1A，纤维蛋白原及血细胞对其不吸附。肝脏药物代谢酶的生物转化作用是MAF-1A的代谢途径之一。MAF-1A的HPLC测量法专属性及稳定性好，能够用于其药代动力学研究。关键词：抗菌肽、药物代谢动力学、HPLC贵阳医学院2013届硕士研究生论文4前言传统抗生素造成耐药株不断

8、地产生，寻求新的抗菌药物迫在眉睫。抗菌肽作为生物体的重要免疫分子，具有可以避免病原体的耐药性及广谱的抗菌活性的特点而倍受青睐。细菌、真菌、植物和动物都能产生序列和结构各异的抗菌肽。其具有高效、[2][3]选择毒性、稳定及不易产生抗药等特点。研究表明抗菌肽还具有抗肿瘤；免[4][5]疫调节和抗病毒作用。由于抗菌肽所特有的优越性，越来越多的抗菌肽被开发或正在开发