ALPPS一期术后肝内干/祖细胞的变化及其与肝再生的关系
| 作者: |
1,2黄民,
1,2黄粲宸,
2肖乐,
2王涛,
2冯亚星,
1,2刘卫辉
1 西南医科大学，四川 泸州 646000 2 中国人民解放军成都军区总医院 全军普通外科中心，四川 成都 610083 |
| 通讯: |
刘卫辉
Email: audiliu12@163.com |
| DOI: | 10.3978/.2018.02.013 |
| 基金: | 四川省杰出青年基金资助项目（2015JQ0001）。 |
摘要
目的：探讨肝内干/祖细胞在联合肝脏分割和门静脉结扎二步肝切除术（ALPPS）一期手术后肝再生中的作用。
方法：将72只SD大鼠随机均分为ALPPS组、门静脉结扎（PVL）组和假手术组，分别行ALPPS一期手术、单纯PVL和假手术。分别在术后1、2、3、7 d检测各组血清转氨酶、炎症因子水平与肝右中叶肝再生率（HRR），并检测肝脏组织中细胞增殖指标Ki-67与肝内卵圆细胞（干/祖细胞）标志物OV-6表达水平。
结果：与假手术组比较，ALPPS组与PVL组术后1~2 d的转氨酶与炎症因子水平均明显升高，且在ALPPS组的升高水平均大于PVL组（均P<0.05）；ALPPS组与PVL组术后肝右中叶HRR及肝组织Ki-67阳性率明显升高，但ALPPS组在术后3、7 d的HRR明显高于PVL组，术后2、3 d的Ki-67阳性率明显高于PVL组（均P<0.05）；ALPPS组与PVL组术后肝组织均有明显OV-6表达，但ALPPS组术后2、3 d的OV-6表达水平明显高于PVL组（均P<0.05）。
结论：ALPPS一期手术诱导的肝再生明显优于PVL，机制可能为ALPPS术后较高的炎症状态使激活肝内干/祖细胞的动员和活化，从而促进快速肝再生有关。
关键词：
肝切除术；肝再生；干细胞；模型，动物；大鼠
方法：将72只SD大鼠随机均分为ALPPS组、门静脉结扎（PVL）组和假手术组，分别行ALPPS一期手术、单纯PVL和假手术。分别在术后1、2、3、7 d检测各组血清转氨酶、炎症因子水平与肝右中叶肝再生率（HRR），并检测肝脏组织中细胞增殖指标Ki-67与肝内卵圆细胞（干/祖细胞）标志物OV-6表达水平。
结果：与假手术组比较，ALPPS组与PVL组术后1~2 d的转氨酶与炎症因子水平均明显升高，且在ALPPS组的升高水平均大于PVL组（均P<0.05）；ALPPS组与PVL组术后肝右中叶HRR及肝组织Ki-67阳性率明显升高，但ALPPS组在术后3、7 d的HRR明显高于PVL组，术后2、3 d的Ki-67阳性率明显高于PVL组（均P<0.05）；ALPPS组与PVL组术后肝组织均有明显OV-6表达，但ALPPS组术后2、3 d的OV-6表达水平明显高于PVL组（均P<0.05）。
结论：ALPPS一期手术诱导的肝再生明显优于PVL，机制可能为ALPPS术后较高的炎症状态使激活肝内干/祖细胞的动员和活化，从而促进快速肝再生有关。
Alteration in intrahepatic stem/progenitor cells after first stage of ALPPS and its relationship to liver regeneration
CorrespondingAuthor:LIU Weihui Email: audiliu12@163.com
Abstract
Objective: To investigate the role of intrahepatic stem/progenitor cells in liver regeneration after the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).
Methods: Seventy-two SD rats were equally randomized into ALPPS group, portal vein ligation (PVL) group and sham operation group, and then underwent the first stage of ALPPS, PVL alone and sham operation, respectively. The serum levels of transaminases and inflammatory factors and the hepatic regeneration rate (HRR) of the right middle lobe of the liver were determined, and the expressions of cell proliferation index Ki-67 and OV-6, the biomarker of oval cells (stem/progenitor cells), were also examined in each group of rats at postoperative day (POD) 1, 2, 3 and 7, respectively.
Results: Compared with sham operation group, the serum levels of transaminases and inflammatory factors were significantly increased in both ALPPS group and PVL group on POD 1 to 2, and their increasing amplitudes in ALPPS group were all significantly higher than those in PVL group (all P<0.05); the HRR of the right middle lobe of the liver and positive Ki-67 rate in the liver tissue were significantly increases in both ALPPS group and PVL group, but the HRR was significantly higher on POD 3 and 7, the positive Ki-67 rate was significantly higher on POD 2 and 3 in ALPPS group than those in PVL group (all P<0.05); obvious OV-6 expression was seen in either ALPPS group or PVL group, but its expression levels in ALPPS group were significantly higher than those in PVL group on POD 2 and 3 (both P<0.05).
Conclusion: The first stage of ALPPS is superior to single PVL for inducing liver regeneration, and the mechanism is probably related to higher inflammatory status after ALPPS which may cause the mobilization and activation of the intrahepatic stem/progenitor cells, and thereby promote the rapid liver regeneration.
Keywords：
Hepatectomy; Liver Regeneration; Stem Cells; Models
Animal; Rats
Methods: Seventy-two SD rats were equally randomized into ALPPS group, portal vein ligation (PVL) group and sham operation group, and then underwent the first stage of ALPPS, PVL alone and sham operation, respectively. The serum levels of transaminases and inflammatory factors and the hepatic regeneration rate (HRR) of the right middle lobe of the liver were determined, and the expressions of cell proliferation index Ki-67 and OV-6, the biomarker of oval cells (stem/progenitor cells), were also examined in each group of rats at postoperative day (POD) 1, 2, 3 and 7, respectively.
Results: Compared with sham operation group, the serum levels of transaminases and inflammatory factors were significantly increased in both ALPPS group and PVL group on POD 1 to 2, and their increasing amplitudes in ALPPS group were all significantly higher than those in PVL group (all P<0.05); the HRR of the right middle lobe of the liver and positive Ki-67 rate in the liver tissue were significantly increases in both ALPPS group and PVL group, but the HRR was significantly higher on POD 3 and 7, the positive Ki-67 rate was significantly higher on POD 2 and 3 in ALPPS group than those in PVL group (all P<0.05); obvious OV-6 expression was seen in either ALPPS group or PVL group, but its expression levels in ALPPS group were significantly higher than those in PVL group on POD 2 and 3 (both P<0.05).
Conclusion: The first stage of ALPPS is superior to single PVL for inducing liver regeneration, and the mechanism is probably related to higher inflammatory status after ALPPS which may cause the mobilization and activation of the intrahepatic stem/progenitor cells, and thereby promote the rapid liver regeneration.