肝硬化大鼠行肝大部切除术后入肝血流对肝功能以及肝脏再生的影响

The effects of liver blood inflow on liver function and liver regeneration after major hepatectomy in the cirrhosis rats

目的研究肝硬化大鼠行肝大部切除术后入肝血流对肝功能以及肝脏再生的影响。方法通过连续8周腹腔注射CCl4构建大鼠肝硬化模型,并在此基础上行肝大部切除术,分别缩窄门静脉和(或)肝动脉,建立不同流量的入肝血流模型,分成对照组、门静脉低流量+肝动脉高流量组、门静脉低流量+肝动脉低流量组、门静脉高流量+肝动脉高流量组、门静脉高流量+肝动脉低流量组,每组7只大鼠。检测不同时间点大鼠肝功能指标的变化、肝脏组织的病理变化,采用免疫组化方法检测各组肝细胞中Ki-67蛋白的表达,并对残余肝脏重量进行对比,判断不同状态的入肝血流对肝脏再生的影响。结果肝大部切除+入肝血流调整后,门静脉低流量组肝细胞间充血减轻,细胞损伤明显减轻;门静脉低流量+肝动脉高流量组大鼠术后第1、3、5天血清ALT分别为(460.9±31.7)U/L、(331.0±22.0)U/L和(285.6±15.8)U/L;同时间点TBIL分别为(20.4±1.5)μmol/L、(16.1±1.0)μmol/L和(13.5±0.6)μmol/L;与对照组比较,均差异明显(P<0.05)。术后第5天,门静脉低流量+肝动脉高流量组、门静脉低流量+肝动脉低流量组及门静脉高流量+肝动脉高流量组大鼠肝细胞中Ki-67表达显著增强[分别为(23.9±3.6)%、(15.7±2.3)%、(12.9±2.4)%],与对照组(10.1±2.1)%相比差异明显(P<0.05),而门静脉高流量+肝动脉低流量组Ki-67表达阳性率(6.1±1.4)%明显低于对照组(P<0.05)。门静脉低流量+肝动脉高流量组术后第5天残余肝脏重量为(15.4±1.0)g,与对照组(11.8±0.7)g相比差异明显(P<0.05)。结论肝硬化大鼠行肝大部切除术后,降低门静脉血流量有助于减轻肝组织的充血,改善肝功能指标;肝细胞再生指标Ki-67表达显著增加,残余肝脏重量明显增加。

Objective To investigate the effect of liver blood inflow on liver function and liver regeneration after major liver resection in the cirrhosis rats.Methods Rat cirrhosis model was constructed through 8-week continuous intraperitoneal injection of carbon tetrachloride（CCl4）.After major liver resection,the different hepatic blood inflow models were established by the stenosis of portal vein and（or） hepatic artery,then rats were randomly assigned to Control group,low-flow PV＋high-flow HA group,low-flow PV＋low-flow HA group,highflow PV＋high-flow HA group,and high-flow PV＋low-flow HA group,7 rats in each group.The liver function was analyzed at different time points,HE staining was performed to observe the pathological status of liver tissue;the liver regeneration was determined by the expression of Ki-67 protein and the weight of remnant liver after sacrifice of the rats was calculated.Results Five days after major liver resection and liver blood inflow modulation,the low-flow PV＋low-flow HA group and low-flow PV＋high-flow HA group showed less intercellular congestion,and less hepatocellular injury.The ALT levels in low-flow PV＋high-flow HA group at day 1,3,5 after liver resection and blood flow modulation were [（460.9±31.7）U/L,（331.0±22.0）U/L and（285.6±15.8）U/L],and the corresponding TBIL levels were [（20.4±1.5）μmol/L,（16.1±1.0）μmol/L and（13.5±0.6）μmol/L],the difference were all significant compared with the control group（P〈0.05）.The positive rates of Ki-67 protein in the hepatocyte of Low-flow PV＋high-flow HA group,Low-flow PV＋low-flow HA group High-flow PV＋highflow HA group were（23.9±3.6）%,（15.7±2.3）%,（12.9±2.4）%,respectively,which were significantly higher than control group [（10.1±2.1）%,P〈0.05],but the Ki-67 expression in Low-flow PV＋high-flow HA group（6.1±1.4）% was lower than that in control group（P〈0.05）.The remnant liver weight of Low-flow PV＋high-flow HA group was（15.4±1.0）g,which was higher than that of control group [（11.8±0.7）g,P〈0.05].Conclusion The decreased portal vein blood inflow after major hepatectomy in the cirrhosis rats alleviates the congestion in the liver,improves the pathological status and liver function,which then increases the expression of Ki-67 and promotes the regeneration.