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maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model

查看全文 作　　者：Yi-fan [1]Tong;Ning [1,2]Meng;Miao-qin [3]Chen;Han-ning [1]Ying;Ming [1]Xu;Billy [4]Lu;Jun-Jie [1]Hong;Yi-fan [1]Wang;Xiujun [1]Cai 高影响力作者 机构地区：[1]Department of General Surgery,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310000,Zhejiang Province,China;[2]Department of General Surgery,Second Hospital,School of Medicine,Hangzhou Normal University,Hangzhou 310000,Zhejiang Province,China;[3]Department of Biological Treatment Research Center,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310000,Zhejiang Province,China;[4]National Center for Advancing Translational Science/National Institutes of Health(NIH),Rickville 20850,American Samoa高影响力机构 出　　处：《World Journal of Gastroenterology》索引2018年第24卷第10期,共13页高影响力期刊 基　　金：Supported by the Major Scientific and Technological Project of Zhejiang Province,China,No.2015C03026 摘　　要：AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration. 关 键 词：associating LIVER PARTITION and portal vein LIGATION for staged HEPATECTOMY LIVER regeneration Hepatic PROGENITOR cell Function IMMATURE
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