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目的探讨在大鼠极限90%门静脉分支结扎模型中门静脉压力促进肝再生过程中白介素-6(interleukin 6,IL-6)在肝脏组织中的表达及其与肝细胞增殖作用的关系。方法 72只Sprague-Dawley(SD)雄性大鼠随机分成假手术对照组和门静脉分支结扎实验组。测定术后0.5、1、3、5、7、14d大鼠门静脉压力变化,观察实验组非结扎侧肝脏质量大体变化,光学显微镜下观察非结扎侧肝组织的病理形态变化,用免疫组化方法检测非结扎侧肝细胞的IL-6和增殖细胞核抗原(PCNA)的表达,并进行统计分析。结果①门静脉压力在结扎后立即升高,0.5d达到高峰(P<0.01),随后逐渐下降,7d左右降至正常水平。②非结扎侧肝叶质量逐渐增加,7d达“平台期”;而结扎侧肝叶逐渐萎缩;非结扎侧肝细胞术后3～7d可见较多的分裂象,肝细胞核增大。③非结扎侧肝细胞中PCNA阳性细胞计数与对照组比较,0.5～5d表达增强(P<0.05),以后逐渐恢复正常。④非结扎侧肝叶IL-6的表达量与对照组比较0.5～5d表达增强,术后7～14d恢复至对照组水平(P>0.05)。⑤门静脉压力与非结扎侧肝叶肝细胞PCNA的表达在术后1、3、5d组呈正相关(r分别为0.816、0.774、0.827,P<0.05),在术后14d组呈负相关(r=-0.761,P<0.05);大鼠肝脏PCNA的表达在术后1、14d组与肝内IL-6表达呈正相关(r分别为0.813、0.825,P<0.05)。结论 IL-6蛋白在门静脉压力促进极限门静脉分支结扎致肝再生过程中发挥重要作用。
Objective To investigate the expression of interleukin 6 (IL-6) and its relationship with hepatocyte proliferation in portal vein pressure-induced liver regeneration in a rat model of 90% portal vein ligation in rats. Methods Seventy two Sprague-Dawley (SD) male rats were randomly divided into sham-operated control group and portal vein ligation group. The changes of portal vein pressure were measured at 0.5, 1, 3, 5, 7 and 14 days after operation. The changes of liver mass in non-ligated side of experimental group were observed. The pathological changes of non-ligated side of liver tissue were observed under optical microscope. The expression of IL-6 and proliferating cell nuclear antigen (PCNA) in non-ligated hepatocytes was detected and statistically analyzed. Results ① The pressure of portal vein increased immediately after ligation and reached the peak on 0.5d (P <0.01), then decreased gradually and decreased to normal level on the 7th day. (2) The quality of non-ligated livers increased gradually, reached the plateau on the 7th day, while the livers on the ligation side gradually atrophied. On the 3rd and 7th day after operation, more schizonts were found and the nuclei of hepatocytes increased. ③ The number of PCNA positive cells in non-ligated side hepatocytes increased from 0.5 to 5 days (P <0.05) compared with the control group, and gradually returned to normal afterwards. ④ The expression of IL-6 in the non-ligation side of liver livers increased from 0.5 to 5 days after operation, and returned to the control level from 7 to 14 days after operation (P> 0.05). (5) There was a positive correlation between portal vein pressure and the expression of PCNA in livers of non-ligated side livers at 1, 3 and 5 days after operation (r = 0.816,0.774, 0.827, P <0.05) = -0.761, P <0.05). The expression of PCNA in rat liver was positively correlated with the level of IL-6 in the liver at 1, 14d after operation (r = 0.813,0.825, P <0.05). Conclusion IL-6 protein plays an important role in the process of hepatic regeneration induced by the portal vein pressure-induced portal vein ligation.