低分子肝素对脓毒症大鼠可溶性血栓调节蛋白、可溶性内皮细胞蛋白C受体及可溶性E-选择素的影响

Effect of the low-dose heparin on STM and sE-selectin in septic rats

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 sepsis 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 various time points from abdominal aorta to determine the levels of s TM,s EPCR and s E-selectin expression by enzyme linked immunosorbent assay( ELISA). Results The levels of STM,s EPCR and s E-selectin expressions had no significant differences among control and sham operation groups( both P>0. 05). STM,s EPCR and s E-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,s EPCR and s E-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 s TM and s E-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.