DMN致小鼠肝损害凝血系统改变及复方肝毒清的干预作用

Pathological changes of coagulation system in DMN-damaged mouse liver and the intervention effect of Chinese herb complex Ganduqing

目的观察二甲基亚硝胺(DMN)诱导的小鼠肝损伤模型凝血系统改变及中药的影响。方法以DMN腹腔注射造模,观察凝血酶原时间(PT)、凝血酶原活动度(PTA)、肝组织凝血因子mRNA、凝血调控因子u-PA、t-PA、PAI-1、TAFImRNA量动态变化;并另取小鼠造模分组灌胃给药,观察复方肝毒清对u-PA、t-PA、PAI-1、TAFI mRNA的影响。结果 DMN造模后PT逐渐延长,48～96h时最长;PTA减小,36～96h之间均小于40%;F2、F11 mRNA造模后有显著升高,均在72h时达到最高;u-PA和t-PA mRNA均明显升高;PAI-1和TAFImRNA均显著降低。复方肝毒清能使PT缩短、PTA升高至40%以上、u-PA和t-PAmRNA水平显著下降、PAI-1和TAFI mRNA明显升高。结论 DMN诱导的肝损伤小鼠凝血系统有明显变化,中药复方可能主要是通过影响凝血纤溶调控因子表达而改善DMN诱导的小鼠肝损伤凝血系统的作用。

Objective To observe the changes of coagulation system in dimethylnitrosamine （DMN） damaged liver and the effects of Chinese herb complex Ganduqing. Methods Liver injury mouse model was established by intraperitoneal injection of DMN. The dynamic changes of prothrombin time （PT）, prothrombin activity （PTA）, mRNA of coagulation factors and coagalation-fibrinolysis modulating factors include u-PA, t-PA, PAI-1, and TAFI were tested. Additionally, another group of mice were administrated with Chinese herb complex Ganduqing and the levels of mRNA of u-PA, t-PA, PAI- 1, and TAFI in the liver tissue were measured. Results The prothrombin time was extended and the longest PT occurred between 48-96 h post modeling. Prothrombin activity was reduced and the value was lower than 40% between 36~96 h post modeling. The mRNA level of coagulation factor 2 and 11 were significantly elevated and reached a maximum at 72 h post modeling. The mRNA levels of u-PA and t-PA was also significantly elevated and the mRNA levels of PAI-1 and TAFI were decreased. The Chinese herb complex Ganduqing administration could shorten the prothrombin time and increase the prothrombin activity to more than 40%. It could also significantly decrease the mRNA levels of u-PA and t-PA, and increase the mRNA levels of PAI-1 and TAFI in the DMN-injured liver. Conchmion There were a significant change in the coagulation system in DMN- injured mouse liver. The promotion effects of Chinese herb complex Ganduqing to the coagulation system may be caused by modulating the expression of coagulation-fibrinolysis modulating factors.