血必净注射液对脓毒症大鼠单核细胞组织因子及凝血功能的影响

Effects of Xuebijing injection on tissue factor of monocytes and coagulation parameters in septic rats

目的 观察血必净注射液对盲肠结扎穿孔术（CLP）所致脓毒症大鼠单核细胞组织因子及凝血功能的影响.方法 将104只Wistar大鼠随机分为正常组、假手术组、CLP组和血必净组,后3组按活杀时间再分为手术后12、24、48、72 h 4个亚组,每组8只.各组于相应时间点经腹主动脉取血,采用流式细胞仪检测单核细胞蛋白酶激活受体-1（PAR-1）的平均荧光强度,采用酶联免疫吸附试验（ELISA）检测血浆组织因子（TF）和肿瘤坏死因子（TNF）-α蛋白含量,并观察凝血活酶时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）的变化.结果 CLP组大鼠单核细胞PAR-1（24、48、72 h分别为21.87±1.08、24.23±0.70、29.70±0.40）、血浆TF[24、48、72 h分别为（505.24±82.82）、（695.43±138.89）、（342.86±16.29）ng/L]、TNF-α水平均较正常组、假手术组显著升高（P〈0.05或P〈0.01）,血必净组町显著降低PAR-1（48、72 h分别为21.47±1.76、19.59±0.17,P〈0.05或P〈0.01）、TF[24、48、72 h分别为（266.67±9.29）、（280.71±41.25）、（253.93±15.31）ng/L,P〈0.05或P〈0.01]、TNF-α水平（P〈0.05或P〈0.01）,并恢复PT、APTT、FIB至正常范围.结论 血必净注射液通过降低单核细胞PAR-1、TF水平改善脓毒症动物凝血功能紊乱.

Objective To investigate the effects of Xuebijing injection on tissue factor （TF） of monocytes and coagulation parameters in septic rats.Methods One hundred and four healthy Wistar rats were randomly divided into four groups：normal group,sham-operation group,cecal ligation and puncture （CLP）group,and Xuebijing-treated group.The three latter groups were divided into 12,24,48,and 72 h subgroups with 8 rats each.The animals were subjected to sepsis induced by CLP.Blood samples of each group were obtained from abdominal aorta.Protease activated receptor-1（PAR-1） of monocytes was assessed by flow cytometer,and enzyme-linked immunoadsorbent assay （ELISA） was used to determine the levels of serum tissue factor and tumor necrosis factor-α（TNF-α）.Meanwhile,prothrombin time （PT）,activated partial thromboplastin time （APTT） as well as fibrinogen （FIB） values were also examined.Results As compared with normal and sham-operation groups,the mean fluorescence intensity of monocytic PAR-1 （21.87±1.08,24.23±0.70,and 29.70±0.40 at 24,48,and 72 h,respectively） and plasma levels of TF [（505.24±82.82）,（695.43±138.89）,and（342.86±16.29）ng/L at 24,48,and 72 h,respectively],and TNF-α were significantly increased in CLP group（P〈0.05 or P〈0.01）.After treatment with Xuebijing injection,however,levels of PAR-1[（21.47±1.76）,（19.59±0.17）at 48,72 h,respectively],TF[（266.67±9.29）,（280.71±41.25）,and（253.93±15.31）ng/L at 24,48,and 72 h,respectively],and TNF-α were markedly decreased compared to CLP group（P〈0.05 or P〈0.01）.In addition,coagulation parameters including PT,APTT,FIB values retuned to the normal range in Xuebijing-treated group.Conclusion Xuebijing injection could obviously ameliorate the coagulation dysfunction and inhibit inflammatory cytokine release through reducing TF and PAR-1 of monocytes.