摘要
目的观察丰宫并殖吸虫所致的大鼠肝脏损伤时MMP-1及其抑制剂TIMP-1在肝纤维形成过程中的动态表达,从而反映其在肝纤维化中的作用机理.方法 SD大鼠25只,随机分为2组.即正常对照组5只和感染组20只.感染组按感染时间长短分为4组,每组5只(感染3周组、感染5周组、感染7周组、感染9周组).感染组每只大鼠腹腔注射8条丰宫并殖吸虫后尾蚴建立动物模型,对照组每只大鼠腹腔注射等量的生理盐水.按感染时间处死各组大鼠.通过ELISA法检测大鼠血清中的MMP-1,TIMP-1含量.同时取肝组织行HE染色判断肝组织发炎程度及肝纤维化程度,行免疫组化染色测MMP-1,TIMP-1在肝组织的表达水平.结果 HE染色肝组织病理形态学结果显示:随着感染时间的延长,肝部炎症逐渐加重,以感染后5周最为明显,之后肝细胞变性坏死逐渐增多.免疫组织化学显示:随病情进展,MMP-1、TIMP-1的表达都是持续上升的.ELISA法所检测的血清中的MMP-1呈现上升的趋势,TIMP-1含量是持续上升的.结论丰宫并殖吸虫感染大鼠可引起肝脏纤维化病变,MMP-1和TIMP-1在此病变过程中的表达有所差异.肝脏病变的严重程度与感染时间、MMP-1和TIMP-1的表达有关.提示MMP-1和TIMP-1在丰宫并殖吸虫感染大鼠致肝纤维化的形成机制中起作用.
Objective To investigate the dynamic changes of MMP-1 and TIMP-1 in rats infected with Paragonimus proliferus,and explore the roles of MMP-1 and TIMP-1 in liver fibrosis formation.Methods Twenty-five SD rats were randomly assigned into two groups： the control group（5 rats） and infection group（20 rats）.The animal model were set up by the way of peritoneal injection of 8 P.proliferus cercarias to each rat in the infection group,while the equal amount of normal saline was injected to each rat in the control group.Infection group were divided into 4 groups according to infection time： at the 3rd,5th,7th and 9th week after infection,5 rats each group.All rats were killed in corresponding time points after being infected.The levels of MMP-1 and TIMP-1 in the serum were determined by enzyme-linked immunosorbent assay.The liver tissues were sectioned and dyed by HE to determine the extent of alveolitis and liver fibrosis.The protein expressions of MMP-1 and TIMP-1 in rat liver parenchyma were detected by immunohistochemistry.Results The results of HE staining： with prolonged infection time,the inflammation increased gradually in the liver tissue of rats,especially at the 5 th week,then liver cell degeneration necrosis increased gradually.The immunohistochemistry showed：with the progression of pathological changes,expressions of MMP-1 and TIMP-1 were increased gradually.Levels of MMP-1 and TIMP-1 detected by ELISA in the serum were increased,and the expression of TIMP-1 was continuously increasing.Conclusions P.proliferus could cause liver fibrosis in rats.Expressions of MMP-1 and TIMP-1 were different during the liver fibrosis formation.The extent of liver lesion was associated with the infection time and the expressions of MMP-1 and TIMP-1.MMP-1 and TIMP-1 played a role in liver fibrosis of rats infected with P.proliferus.
出处
《昆明医科大学学报》
CAS
2013年第3期26-30,40,共6页
Journal of Kunming Medical University
基金
云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(2012FB025)
