脓毒症模型大鼠循环内皮细胞与肝功能状态间关系的相关性研究

Correlation between circulating endothelial cell and hepatic functional status in rat model of sepsis

目的探讨大鼠脓毒症中循环内皮细胞(circulating endothelial cells,CEC)数量的变化及其与肝功能改变的关系。方法利用盲肠结扎穿孔模型(CLP)在大鼠制作脓毒症模型。观察CEC数量、白细胞数量的变化、以及肝组织病理组织学、血天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)的改变。并探讨CEC数量与AST和ALT的相关关系。结果CLP6h后动物肝细胞明显肿胀,24h组肝细胞大量空泡变性,乃至坏死。CLP3h组白细胞和CEC数量比对照组明显升高。而CLP6h后AST、ALT才出现明显增高。CEC数量与AST和ALT水平呈负相关,Pearson相关系数(r)分别为-0·774和-0.734(P<0·01)。用非线性回归分析CEC数量与AST和ALT的关系,发现CEC数量对ALT的最佳拟合曲线为幂函数(P<0·05),其方程为ALT=33.052681+24.097309CEC-1。CEC数量对AST的最佳拟合曲线为对数函数,但无统计学意义(P=0.607)。结论在大鼠脓毒症模型中,比起常规肝功能指标,CEC数量更能敏感反映肝脏病理进程。当肝功能指标高于正常阈值时肝细胞已经出现了显著损伤。因此,早期监测CEC数量结合已有的肝功能指标有助于早期提示肝功能损害,及时针对治疗。

Objective To investigate the relationship between the number of circulating endothelial Cells （CEC） and the hepatic functional change in the sepsis rats. Methods The model of sepsis was established by cecal ligation and puncture （CLP） in rats. The number of WBC, CEC were counted at different time points after CLP. Meanwhile, serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were examined and the histologic changes of hepatic tissue were observed. Then the correlations were analyzed between CEC number and the levels of serum AST and ALT respectively. Results Engorgement, degeneration and even necrosis were observed gradually after CLP in hepatocytes. The number of WBC and CEC in 3 h after CLP were significantly higher than that in sham group. The levels of AST and ALT increased notably in 6 h after CLP as compared with that of the normal controls. The number of CEC was negatively correlated to AST, ALT respectively. The Pearson＇ s correlation coefficients （r）, were -0.774 and -0.734 （P 〈 0. 01 ）. The nonlinear regression analysis showed that power function was the best when fitted ALT with CEC number （P 〈 0. 05）. Equation was ALT = 3. 052 681 ＋ 24.097 309 CEC ^- 1. The best fitting plot was logarithmic function between CEC number and AST. But it had no statistical significance （ P = 0. 607 ）. Conclusion CEC number reflects hepatic status more sensitive as compared with routine hepatic functional parameters. The hepatocytes have been damaged significantly when the routine parameters are above the threshold value. So monitoring CEC number and hepatic functional parameters simultaneously could help find hepatic damage earlier and thus start hepatocyte-protective therapy as early as possible.