目的探讨低分子肝素对脓毒症大鼠肺血管内皮细胞功能的影响。方法采用大鼠盲肠结扎穿孔术(CLP)复制大鼠脓毒症模型。清洁级雄性Wistar大鼠104只被随机分为正常对照组、假手术组、脓毒症模型组和低分子肝素治疗组,每组8只,其中后三组按术后处死时间分为12、24、48、72 h共4个亚组。各组分别在相应时间点处死大鼠,经腹主动脉取血进行常规检测,用酶联免疫吸附法(ELISA)测定可溶性血栓调节蛋白(s TM)、可溶性内皮细胞蛋白C受体(s EPCR)浓度以及炎症反应可溶性E-选择素(s E-selectin)的含量。结果正常对照组和假手术组s TM、s EPCR和s E-selectin的表达水平均无显著差异(P均>0.05)。脓毒症模型组伤后12 h开始在各个时间点s TM、s EPCR和s E-selectin的表达均有不同程度增高(P均<0.05),并持续至伤后72 h;与模型组比较,低分子肝素治疗组于CLP后12 h开始,至24、48 h,s TM、s EPCR和s E-selectin的表达均明显降低,并持续至72 h(P均<0.05)。结论低分子肝素能通过对脓毒症凝血-炎症网络的调节,降低脓毒症大鼠s TM的表达水平,并降低大鼠体内s E-selectin的水平,从而减轻肺组织炎症损害,在一定程度上缓解脓毒症的进程。
Objective To investigate the effects of low-dose heparin injection on pulmonary vascular endothelial cell function of sep-sis rats.Methods Sepsis model was produced by cecal ligation and puncture(CLP).104 healthy male Wistar rats were randomly divided into control,sham operation,cecal ligation and puncture(CLP) model group,and low-dose heparin-treated groups.The three latter groups were divided into four subgroups of 12,24,48 and 72 h with 8 rats in each subgroup.The blood samples of each group were collected at vari-ous time points from abdominal aorta to determine the levels of sTM,sEPCR and sE-selectin expression by enzyme linked immunosorbent as-say( ELISA) .Results The levels of STM,sEPCR and sE-selectin expressions had no significant differences among control and sham opera-tion groups(both P>0.05).STM,sEPCR and sE-selectin expressions levels were significantly increased beginning at 12 h in post-CLP(all P<0.05),and were decreased continuing at 72 h.Also,low-dose heparin dramatically decreased STM,sEPCR and sE-selectin levels at 12 h, and markedly decreased at 48 and 72 h compared with those of model group(all P<0.05).Conclusions Low molecular heparin could pass to sepsis coagulation-inflammation network adjustment,reduce the expression levels of sTM and sE-selectin in sepsis rats so as to reduce the inflammation of lung tissue damage,and it could obviously alleviate the development of sepsis at a certain extent.