人CYP2D6诱导小鼠自身免疫性肝炎动物模型的建立  

Establishment of a mouse model of autoimmune hepatitis induced by human CYP2D6

作　　者：池刚[1] 马沁雅 裴晋红[1] 冯作化[3] CHI Gang;MA Qinya;PEI Jinhong;FENG Zuohua(Department of Biochemistry,Changzhi Medical College,Changzhi 046000;Changzhi Public Security Bureau,Changzhi 046000;Huazhong University of Science and Technology,Wuhan 430074,China)

机构地区：[1]长治医学院生化教研室 [2]长治市公安局,山西长治046000 [3]华中科技大学,湖北武汉430074

出　　处：《细胞与分子免疫学杂志》2018年第8期690-694,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81472704)

摘　　要：目的研究模拟抗原人细胞色素P450家族2亚家族D成员6(CYP2D6)和遗传背景差异的小鼠(C57BL/6和BALB/c)对自身免疫性肝炎(AIH)动物模型建立的影响。方法 C57BL/6和BALB/c小鼠尾静脉注射腺病毒及质粒p CYP2D6,用ELISA检测血清抗CYP2D6抗体和抗肝蛋白自身抗体水平; HE染色检测肝脏AIH炎症程度,天狼猩红染色检测肝纤维化的程度;微孔板法检测血清丙氨酸转氨酶(ALT)的水平。结果腺病毒促进人CYP2D6诱导C57BL/6小鼠产生抗肝蛋白自身抗体、并引起AIH和肝纤维化,而在BALB/c小鼠中,仅产生针对人CYP2D6的抗体,而无抗肝蛋白自身抗体、不产生AIH和肝纤维化。结论在腺病毒存在下,模拟抗原人CYP2D6在肝脏中的持续表达可以诱导C57BL/6小鼠产生AIH,但是无法诱导BALB/c小鼠产生AIH,不同品系小鼠的遗传背景可能影响着AIH的发生发展。Objective To investigate the effect of human cytochrome P450 family 2 subfamily D member 6( CYP2 D6) on the establishment of animal model of autoimmune hepatitis( AIH) in C57 BL/6 and BALB/c mice. Methods Adenovirus( Ad) and plasmid p CYP2 D6 were injected into the tail vein of mice. Serum anti-CYP2 D6 antibody and hepatic protein( HP)autoantibody were detected by ELISA. HE staining was used to detect the degree of liver AIH inflammation,and the degree of liver fibrosis was detected by sirius red staining. The level of alanine aminotransferase( ALT) was determined by microplate method. Results Ad and self-mimicking antigen( human CYP2 D6) induced the secretion of HP autoantibody,AIH,hepatic injury and liver fibrosis in C57 BL/6 mice,whereas only anti-CYP2 D6 antibody was generated in BALB/c mice;no HP autoantibody,AIH or liver fibrosis was induced. Conclusion In the presence of AD,the continuous expression of self-mimicking antigen( human CYP2 D6) could induce AIH in C57 BL/6 mice,but not in BALB/c mice. Thus,the genetic background in the different strains of mice could influence the occurrence and development of AIH.

关 键 词：分子模拟 遗传背景 自身免疫性肝炎(AIH) 动物模型 

分 类 号：Q311[生物学—遗传学] R575.1[医药卫生—消化系统]