Xu Yinzhe, Navarro-Alvarez Nalu, Yang Chao, Markmann James F, Dong Jiahong, Yeh Heidi
Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China; Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
J Surg Res. 2016 Jul;204(1):75-82. doi: 10.1016/j.jss.2016.03.066. Epub 2016 Apr 9.
Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours.
A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining.
Retrospective analysis indicated that body condition scores ≤5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes.
Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration.
肝切除术后肝衰竭及其移植对应情况，即小肝综合征，仍然是肝切除和节段性肝移植的重大限制因素。小鼠部分肝切除术是研究肝再生最常用的模型之一，但收集数据所需的血液和组织采样会影响结果，甚至可能需要实施安乐死。因此，我们开发了一种定量观察系统，以预测术后24小时内肝切除术后的死亡情况。
总共100只10至12周龄的雌性C57BL/6小鼠接受了三分之二肝切除术，并监测长达7天。我们的评分系统基于五个类别，每个类别给予0至2分：活动水平、身体姿势、皮毛状况、呼吸状态和眼睛外观。75只小鼠在术后6小时、12小时、24小时、2天、3天、5天和7天进行评分。其余25只小鼠进行类似评分，但另外还进行了血清丙氨酸氨基转移酶、总胆红素、白细胞介素-6、肿瘤坏死因子-α的血液采样，或实施安乐死并进行肝脏采样以进行常规苏木精-伊红染色和Ki-67染色。
回顾性分析表明，术后24小时内连续两个时间点的身体状况评分≤5可准确预测最终死亡。低评分组的动物血清丙氨酸氨基转移酶、总胆红素、白细胞介素-6、肿瘤坏死因子-α也显著更高，苏木精-伊红染色显示肝细胞坏死更多，Ki-67阳性肝细胞更少。
我们的评分系统可在手术的前24小时内准确预测小鼠肝切除模型中的生存情况、肝细胞损伤、肝再生和全身炎症反应。这对于评估肝切除术后干预措施对生存和肝再生的影响可能有用。
