毒热平注射液对流感病毒性肺炎小鼠肺组织MMP-9及TIMP-1含量的影响

Effects of Dureping Injection on the Contents of MMP-9 and TIMP-1 in the Lung Tissue of Mice with Pneumonia of Influenza Virus Infection

目的观察毒热平注射液对流感病毒性肺炎小鼠肺组织中基质金属蛋白酶9(matrix metallopro-teinase-9,MMP-9)及基质金属蛋白酶抑制物1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)的影响。方法 66只ICR小鼠随机分为正常组、模型组、毒热平低剂量组(0.435mg/d)、中剂量组(0.870mg/d)、高剂量组(1.740mg/d)和利巴韦林对照组(对照组,2.500mg/d),每组11只。以经鼻吸入流感病毒亚洲甲型鼠肺适应株(FM1)复制小鼠流感病毒性肺炎模型。感染后当日开始腹腔注射给药,0.3mL/次,1次/天。5天后处死小鼠,计算肺指数;制作切片,光镜观察肺组织病理形态变化;采用ELISA双抗体夹心法测定肺组织匀浆液中MMP-9及TIMP-1含量。结果与正常组比较,模型组小鼠肺组织出现明显炎性病变,其肺指数、肺组织MMP-9及MMP-9/TIMP-1显著升高(P<0.01),而TIMP-1含量变化不明显(P>0.05);与模型组比较,毒热平低、中剂量组和对照组MMP-9降低(P<0.01),各剂量组和对照组TIMP-1升高(P<0.01),MMP-9/TIMP-1降低(P<0.01)。结论毒热平注射液可通过降低流感病毒性肺炎小鼠肺组织中MMP-9含量,提高TIMP-1含量,调节两者比值,从而减轻肺组织炎性损伤。

Objective To observe the effects of Dureping Injection on the contents of matrix metalloproteinase-9（MMP-9） and tissue inhibitor of matrix metalloproteinase-1（TIMP-1） in the lung tissue of mice with pneumonia of influenza virus infection. Methods Sixty-six ICR mice were randomly divided into the normal group,the model group,the low,middle,and high dose Dureping Injection groups（0.435,0.870,and 1.740 mg/d,respectively） ,and the positive control group（Ribavirin,2.500 mg/d） ,11 in each. The pneumonia of mice with influenza virus infection model was established using influenza virus strain FM1. Mice were intraperitoneally injected with 0.3 mL FM1 starting from the infection day,once daily. Five days later mice were killed to calculate the lung index. The pathomorphological changes of the lung tissue were observed using routine HE stained sections. The contents of MMP-9 and TIMP-1 in the homogenate of the lung tissue were detected by ELISA double antibody sandwich method. Results Compared with the normal group,obvious inflammation occurred in the lung tissue of mice in the model group. The lung index,the content of MMP-9,and the value of MMP-9/TIMP-1 increased significantly in the model group（P0.01） ,while the content of TIMP-1 was not significantly different（P0.05） . Compared with the model group,the content of MMP-9 in the low and middle dose Dureping Injection groups,and the positive control group was significantly lowered（P0.01） . The content of TIMP-1 in the low,middle,and high dose Dureping Injection groups,as well as the positive control group significantly increased（P0.01） and the value of MMP-9/TIMP-1 decreased（P0.01） . Conclusion Dureping Injection could alleviate the inflammatory injury of the lung tissue through decreasing the content of MMP-9,elevating the content of TIMP-1 in the lung tissue,and regulating the value of MMP-9/TIMP-1 of mice with pneumonia of influenza virus infection,thus alleviating the inflammatory injury of the lung tissue.