长期使用邦亭所致的血浆纤维蛋白原降低机制的初步实验研究

摘要

Objective To study the effect of the long-term administration of hemocoagulasein vitro and in vivo,whether it may cause hypofibrinogenemia and changes of cytokine interleukin-6(IL-6) expression level which related to fibrinogen synthesis.Methods Totally 50 healthy subjects pooled plasma was chose in vitro experiments,which was divided into 7 groups.After that,added various of dilutions of injection hemocoagulase and incubated at 37 ℃,detected FIB concentration every 12 h.In vivo experiments,80 rats with six-week old were randomly divided into 4 groups:negative control group,high-dose group,middle-dose group,low-dose group,After 3 weeks administration,the serum level of Ⅴfactor,Ⅷ factor,PT,activated partial thromboplastin time (APTT),FIB,IL-6 was detected.Results Hemocoagulase in vitro had a strong role to reduce fibrin,and showed a significant dose-dependent and time-dependent;Hemocoagulase prolonged low-dose use might reduce the concentration of FIB in mice,but theⅤfactor,Ⅷ factor,PT,APTT,TT were not significantly affected.Compared with the negative control group,FIB and IL-6 concentration decreased in high-dose group,middle-dose group,low-dose group and had statistically significant differences (P<0.05);The level of FIB among the groups had statistically significant differences (P<0.05).The APTT of the middle and high dose groups was slightly prolonged,which was significantly different from that of the negative control group (P<0.05).Conclusion Hemocoagulase has a strong effect to reduce the concentration of fibrin,when there is a long-term medication,fibrin concentration of the patient should be closely monitored,hemocoagulase not only directly decomposed fibrin,but also may affect the synthesis of IL-6,the specific mechanism needs further study.%目的 研究邦亭体内外降低血浆纤维蛋白原(FIB)及对与FIB合成相关的细胞因子白介素-6(IL-6)表达水平的影响.方法 体外实验随机选取50份健康体检者混合血浆充分混匀后,随机平均分为7组,加入不同水平稀释的邦亭注射液后置于37 ℃温箱孵育,每12 h检测FIB水平;动物实验选取6周龄健康昆明小鼠80只,雌雄各半,随机分为阴性对照组、低剂量组、中剂量组、高剂量组,每组20只,雌雄各半.各组按剂量腹腔注射邦亭3周后处死,分别检测凝血因子Ⅴ、凝血因子Ⅷ、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、FIB和IL-6水平.结果 邦亭在体外有很强的降低FIB的作用,并呈现出明显的时间和剂量依赖性;邦亭长时间小剂量使用,可降低小鼠体内的FIB水平,但对凝血因子Ⅴ、凝血因子Ⅷ、PT、凝血酶时间(TT)并无明显影响;与阴性对照组相比,低、中、高剂量组的FIB、IL-6水平均下降,差异有统计学意义(P<0.05);各组间FIB水平比较差异有统计学意义(P<0.05);中、高剂量组的APTT轻微延长,与阴性对照组比较差异有统计学意义(P<0.05).结论 邦亭体内外均有较强的降低FIB的作用,临床长期用药时应密切检测患者的FIB水平,邦亭体内不仅直接分解FIB,可能还影响FIB合成相关的细胞因子水平,其具体机制有待更进一步的研究.