利用基质胶阻断门静脉建立改良ALPPS手术小鼠模型

A Modified ALPPS Mice Model Based on the Blockade of Portal Vein by Matrigel

目的建立一种不依赖显微外科技术的改良联合肝脏分隔和门静脉结扎的二步肝切除(ALPPS)手术小鼠模型,并验证其刺激肝再生的有效性。方法75只C57BL/6小鼠随机分为ALPPS-显微手术(ALPPS-micro)组、ALPPS-基质胶(matrigel)封堵(ALPPS-matri)组和基质胶封堵对照(Control-matri)组。ALPPS-micro组和ALPPS-matri组分别采用显微镜下结扎法和基质胶封堵法阻断门静脉;Control-matri组作为对照,验证手术的有效性和安全性。记录各组手术时间、术中出血以及围手术期生存数据,并采集术后不同时间的血液和肝脏标本;通过计算肝脏质量与体质量比值(肝体比)以及检测增殖相关分子Cyclin D1和Ki-67的表达水平,比较ALPPS-显微手术和ALPPS-基质胶封堵手术对肝脏再生的刺激作用。结果与ALPPS-micro组相比,ALPPS-matri组手术操作时间短[(19.0±4.6)min比(37.5±9.3)min,P<0.05],术中出血量少[(153±39)mL比(317±124)mL,P<0.05],一期术后死亡率更低(4.0%比20.0%,P<0.05)。肝体比数据和增殖相关分子检测结果提示,ALPPS-matri组具有与ALPPS-micro组类似的刺激肝脏再生的效果。结论利用基质胶的改良ALPPS模型与基于显微外科的传统ALPPS模型相比,具有相似的肝脏再生刺激效果,但手术时间更短,术中出血更少,围手术期死亡率更低。

Objective To construct a modified mice model associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) without relying on microsurgical techniques, and to verify its effectiveness in stimulating liver regeneration. Methods Seventy-five adult C57 BL/6 mice were randomly divided into three groups: ALPPS-microsurgery(ALPPS-micro) group, ALPPS-matrigel blocking(ALPPS-matri) group and matrigel blocking control(Control-matri) group. The ALPPS-micro group and the ALPPS-matri group were treated with microscopic ligation and matrigel injection to block the portal vein blood flow, respectively.The Control-matri group served as a control group to verify the effectiveness and safety of this surgery.Data of operation time, intraoperative bleeding and perioperative survival were recorded, and blood and liver samples were collected at different time points after surgery. The effects of different operations on liver regeneration were compared by measuring the ratio of liver weight to body weight(LBR) and detecting the expression levels of proliferation-related molecules Cyclin D1 and Ki-67. Results Compared with the ALPPS-micro group, the ALPPS-matri group had shorter operation time [(19.0±4.6) min vs(37.5±9.3) min,P<0.05], less intraoperative bleeding [(153 ± 39) mL vs(317 ± 124) mL, P<0.05], and lower mortality of Ⅰstage surgery(4.0% vs 20.0%, P<0.05). The detection results of LBR and the expression levels of proliferationrelated molecules suggested that the ALPPS-matri group showed a similar effect on stimulating liver regeneration as the ALPPS-micro group. Conclusion Compared with the traditional microsurgery-based ALPPS model, the modified ALPPS model using matrigel has a similar effect on liver regeneration with shorter operation time, less intraoperative bleeding, and lower perioperative mortality.