MMP-9和TIMP-1在丰宫并殖吸虫感染大鼠致肺纤维化中的表达及意义

Expression and significance of MMP-9 and TIMP-1 in lung fibrosis of rats infected with paragonimusproliferus

目的观察丰宫并殖吸虫感染大鼠致肺损伤时MMP-9及其抑制剂TIMP-1在肺纤维形成过程中的动态表达,探讨MMP-9和TIMP-1在肺纤维化中的作用机理。方法 SD大鼠25只,随机分为两组。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)。在不同的感染时间处死各组大鼠。通过ELISA法检测大鼠血清中的MMP-9,TIMP-1含量。同时取肺组织行HE染色和Masson染色判断肺组织肺泡炎及肺纤维化程度,行免疫组化染色测MMP-9,TIMP-1在肺组织的表达水平。结果 HE染色和Masson染色肺组织病理形态学结果显示:随着感染时间的延长,肺部炎症逐渐加重,之后炎症有所减轻而胶原明显增生。免疫组织化学显示:随病情进展,MMP-9的表达呈现先上升后下降的趋势,而TIMP-1是持续上升的,MMP-9/TIMP-1比值也是先上升后下降的,即MMP-9/TIMP-1比值在肺损伤早期(肺泡炎期)是升高的,在后期(肺纤维化期)是降低的。ELISA法所检测的血清中的MMP-9,TIMP-1含量及其两者的比例也出现类似的变化。结论丰宫并殖吸虫感染大鼠可引起肺脏纤维化病变。肺脏病变的严重程度与感染时间、MMP-9和TIMP-1的表达有关。提示MMP-9和TIMP-1在丰宫并殖吸虫感染大鼠致肺纤维化的形成机制中起作用。

Objective To investigate the dynamic changes of MMP-9 and TIMP-1 in rats infected with paragonimusproliferus,and to explore the mechanism of action of MMP-9,TIMP-1 in lung fibrosis formation.Methods Twenty-five SD rats were randomly divided into two groups:the control group(5 cases)and infection group(20 cases).The rats in infection group were divided into 4 groups according to infection time:at the 3rd,5th,7thand 9th week after infection,5 rats each group.All rats were killed in corresponding time points after being infected.The levels of MMP-9,TIMP-1 in the serum were determined by enzyme-linked immunosorbent assay.The lung tissues were sectioned and dyed by HE and Masson to determine the extent of alveolitis and lung fibrosis.The protein expression of MMP-9,TIMP-1 in rat pulmonary parenchyma were detected by immunohistochemistry.Results The pathomorphological results of lung tissue of HE staining and Masson staining:With prolonged infection time,the inflammation gradually increased in the lung tissue,then inflammation decreased while collagen hyperplasia increased obvious.The immunohistochemistry showed:with the progression of pathological changes,the expression of MMP-9 was increased and then decreased,the expression of TIMP-1 was increased,the ratio of MMP-9/TIMP-1 was also increased and then decreased.Similar changes also occurred in the serum levels of MMP-9,TIMP-1 and their proportions as detected by ELISA.Conclusion The infection of rats with paragonimusfunius can cause lung fibrosis.The severity of lung lesions is related to the time of infection,the expression of MMP-9 and TIMP-1.It is suggested that MMP-9 and TIMP-1 play a role in lung fibrosis of rats infected with paragonimusproliferus.