纤溶酶原激活物抑制剂-1在大鼠肝纤维化模型及自发逆转肝组织中的动态变化及意义  

Dynamic changes and significance of plasminogen activator inhibitor-1 in hepatic fibrosis in rats

作　　者：朱颖炜[1] 龚镭[1] 吴高珏[1] 王要军[2] 林勇[2] 谢渭芬[2] 

机构地区：[1]南京医科大学附属无锡第二人民医院消化内科,江苏无锡214002 [2]第二军医大学长征医院消化内科,上海200003

出　　处：《南京医科大学学报（自然科学版）》2015年第3期357-362,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：无锡市医管中心联合公关项目(YGZX1202)

摘　　要：目的 :探讨纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)在肝纤维化发生、发展及消退过程中的表达变化及意义。方法:采用皮下注射四氯化碳(carbon tetrachloride,CCl4)方法制备大鼠肝纤维化模型,在注射及停止注射后不同时间,取组织标本,HE和Van Gieson氏(简称VG)染色。明确纤维化分期后,利用免疫组化及RT-PCR方法,观察PAI-1在肝纤维化进程及逆转中表达变化情况。结果:在正常大鼠肝脏中,PAI-1仅在汇管区细胞浆有少量表达;在纤维化肝脏,PAI-1主要分布于肝血窦壁及细胞浆。随着纤维化的进展,PAI-1表达量进行性增加(正常对照组为0.142±0.030,模型组注射CCl42、6和8周组分别为0.361±0.048、0.757±0.068和0.838±0.048);肝纤维化自然消退过程中又逐渐减弱(自发逆转2、4和6周组分别为0.613±0.054、0.524±0.060和0.210±0.044)。RT-PCR检测,模型组注射CCl42、6和8周后,PAI-1 m RNA在肝脏组织中的表达分别是正常肝组织的(6.83±2.60)倍、(12.43±2.65)倍和(26.32±5.17)倍,停止注射CCl4后,在自发逆转2、4和6周时,PAI-1 m RNA在肝脏组织中的表达只是正常肝组织中的(17.86±4.60)倍、(14.62±5.99)倍和(11.21±1.98)倍。结论:PAI-1在肝纤维化进程中持续上调,在肝纤维化逆转过程中表达下调,可能在肝纤维化发生发展中起重要作用。Objective：To investigate the role of plasminogen activator inhibitor-l（PAI-1） in the development and spontaneous regression of liver fibrosis. Methods： Rat liver fibrosis models were induced by subcutaneous injection of carbon tetrachloride （CCL） and tissue samples were obtained for study at various times. The different stages of fibrosis were confirmed with HE and VG staining, and then the expression of PAI-1 in these tissue samples was detected by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry. Results：There was only weak expression of PAI-1 detected in endochylema located in portal area of normal liver,and the expression of PAl-1 was mainly located within the area of hepatic sinusoid and endochylema in fibrotic liver. The PAI-1 expression increased accordingly with the development and progression of fibrosis while decreased in spontaneous regression. Semiquantitative analysis showed that the expression of PAI-1 for normal control and 2,4,6 weeks after CC14 administration were 0.142 ± 0.030,0.361 ± 0.048,0.757 ± 0.068 and 0.838 ± 0.048,the expression of PAI-1 for 2,4,6 weeks after resolution of fibrosis were 0.613 ± 0.054,0.524 ± 0.060 and 0.210± 0.044. Semiquantitative analysis by RT-PCR showed that the mRNA expression of PAI-1 in the model group treated with CCl4 for 2,6,8 weeks was higher than that in normal control,increasing to 6.83 ± 2.60,12.43 ± 2.65 and 26.32 ± 5.17 fold. Nevertheless,the mRNA expression of PAI-1 decreased with the resolution of fibrosis after stopping CCl4 induction. The mRNA expression of PAI-1 for 2,4,6 weeks after resolution of fibrosis was 17.86 ± 4.6,14.62 ± 5.99 and 11.21 ± 1.98 times,respectively,compared with normal control. Conclusion：PAI-1 was up-regulated in liver fibrosis development while down-regulated in spontaneous regression, which indicated that it may play an important role in the development and progression of hepatic fibrosis.

关 键 词：纤溶酶原激活物抑制剂-1 纤溶系统 肝纤维化 肝硬化 

分 类 号：R575.2[医药卫生—消化系统]