摘要
目的探讨内质网应激在联合肝脏分割和门静脉结扎二步肝切除术(ALPPS)一期手术后肝再生过程中的作用。方法将72只C57bl/6小鼠随机均分为ALPPS组、门静脉结扎组(PVL组)和假手术组(Sham组),每组24只,分别行ALPPS一期手术、单纯PVL和假手术。3组小鼠分别在术后第1、2、4及7天各取材6只,检测各组小鼠的肝重体质量比,并取肝脏组织行免疫组织化学染色以计算Ki-67阳性细胞比,行Western blot法以检测肌醇酶1α(IRE1α)和X盒连接蛋白1(XBP1)蛋白的表达水平。结果①肝重体质量比:术后第4天和第7天时,同时点下Sham组、PLV组和ALPPS组的肝重体质量比依次增加,3组间两两比较差异均有统计学意义(P<0.05)。②Ki-67阳性细胞比:术后第2天时,Sham组、PLV组和ALPPS组的Ki-67阳性细胞比依次增加,3组间两两比较差异均有统计学意义(P<0.05);术后第4天时,ALPPS组与PVL组的Ki-67阳性细胞比仍高于Sham组(P<0.05)。③XBP1和IRE1α的表达水平:术后第2天和第4天时,与Sham组和PVL组比较,ALPPS组的XBP1和IRE1α的表达水平均较高(P<0.05);术后第7天时,与Sham组比较,ALPPS组的XBP1和IRE1α的表达水平较高(P<0.05);与PVL组比较,ALPPS组的XBP1的表达水平较高(P<0.05)。结论在小鼠体内ALPPS术式诱导的肝再生较传统的PVL术式引起的肝再生更具有优势,这可能是因为ALPPS术后更为明显的内质网应激激活状态,导致IRE1α-XBP1的表达上调,从而参与了肝细胞细胞周期的调控,进而促进了肝细胞的增殖,促进了快速肝再生。
Objective To investigate the role of endoplasmic reticulum stress in liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Methods Seventy-two C57bl/6 mice were randomly divided into ALPPS group, portal vein ligation group (PVL group), and sham operation group (Sham group), 24 mice in each group. And then one-stage ALPPS operation, simple PVL, and sham operation will be performed. Six mice were randomized selected of the three groups on the 1st, 2nd, 4th, and 7th day after surgery, respectively, the liver weight to body weight ratio (FLR/BW) of each group was measured, and the liver tissues were taken for immunohistochemical staining to calculate the proportion of Ki-67 positive cells, Western blot was used to detect the expression levels of X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α(IRE1α) proteins. Results ① FLR/ BW: On the 4th day and the 7th day after operation, the FLR/BW of the Sham group, PVL group, and ALPPS group increased in sequence at the same time, and the difference between the three groups was statistically significant (P<0.05).② Ki-67 positive cell ratio: On the 2nd day after operation, the ratio of Ki-67 positive cells in the Sham group, PVL group, and ALPPS group increased sequentially, and the difference between the two groups was statistically significant (P<0.05). On the 4th day after operation, the ratio of Ki-67 positive cells in the PVL group and the ALPPS group were still higher than that of the Sham group (P<0.05).③ Expression levels of XBP1 and IRE1α: On the 2nd and 4th postoperative day, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group and the PVL group (P<0.05). On the 7th day after surgery, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group (P<0.05), while compared with the PVL group, the expression level of XBP1 in the ALPPS group was still higher (P<0.05). Conclusions ALPPS-induced liver regenerat
作者
龚奇
徐锋
赵亮
戴朝六
GONG Qi;XU Feng;ZHAO Liang;DAI Chaoliu(Department of Hepatobiliary and Splenic Surgery,Shengjing Hospital of China Medical University,Shenyang 110004,P.R.China)
出处
《中国普外基础与临床杂志》
CAS
2019年第10期1162-1169,共8页
Chinese Journal of Bases and Clinics In General Surgery
基金
辽宁省科技厅科学计划项目（项目编号：2017225032）
沈阳市科技局重点科技研发计划项目（项目编号：17-230-9-16)
关键词
肝再生
内质网应激
增殖
联合肝脏分割和门静脉结扎二步肝切除术
X-框结合蛋白1
肌醇酶1α
liver regeneration
endoplasmic reticulum stress
proliferation
associating liver partition and portal vein ligation for staged hepatectomy
X-box binding protein 1
inositol-requiring enzyme 1α
