血吸虫肝纤维化中基质金属蛋白酶及抑制剂的表达

Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in liver tissue with Schistosomiasis Japonica

目的观察基质金属蛋白酶（MMP）-13，基质金属蛋白酶组织抑制剂（TIMP）-3及α-平滑肌肌动蛋白（α-SMA）在晚期日本血吸虫病家兔肝脏和正常家兔肝脏中的表达。方法应用免疫组织化学和半定量Western免疫印迹方法检测了血吸虫病肝纤维化模型家兔42只及正常家兔8只中的MMP-13、TIMP-3、α-SMA的表达。结果正常对照组的MMP-13、TIMP-3、α-SMA的表达分别是（3．20±0.45）、（0．76±0．32）、（0．92±0．28）％；血吸虫病纤维化肝脏中的MMP-13、TIMP-3、α-SMA的表达分别是（10．56±3．62）、（6．50±2．56）、（5．78±2．98）％，较正常对照组明显增加（P〈0．01），主要表达于成纤维细胞，肌成纤维细胞中，以纤维间隔及汇管区最明显，且三者来源定位基本一致。结论在血吸虫病肝纤维化中，成纤维细胞及肌成纤维细胞是MMP-13、TIMP-3、α-SMA表达的主要细胞，TIMP-3的表达增高在肝纤维化的发生、发展中具有重要作用。

Objective To explore the expression and distribution of matrix metalloproteinase （MMP） -13, tissue inhibitor of metalloproteinase （TIMP） -3 and alpha- smooth muscle actin （α-SMA） in liver tissue of the rabbits infected with schistosomiasis japonica and normal ones. Methods Immunohistochemistry and Western blot were applied to detect the protein expression of MMP-13, TIMP-3, α-SMA in 42 schistosomiasis rabbits with liver fibrosis and 8 normal rabbits. Results The protein expression of MMP-13, TIMP-3 and α-SMA in the control group was （3.20 ± 0.45）, （0.76 ± 0.32） and （0.92 ± 0.28）% respectively, and that in in experimental group was （10.56± 3.62）, （6.50± 2.56） and （5.78 ± 2.98 ）% respectively. The expression of MMP-13, TIMP-3 and α-SMA was significantly stronger in liver tissue of the infected rabbits than in the controls （P 〈 0.01 ）. They were mainly expressed in the fibroblasts and myofibroblasts, especially focused in the fibrous and Disse space, and located in the same place. Conclusion The fibroblasts and myofibroblasts are main cells to express MMP-13, TIMP-3 and α-SMA genes, and the increased expression of TIMP-3 plays an important role in the formation of liver fibrosis.