如何降低急性胰腺炎的病死率是一项意义重大的课题。日本2021版诊疗指南提出了对急性胰腺炎患者的“集束化管理措施”,在此指导下,日本急性胰腺炎总体病死率下降至2.6%,重症急性胰腺炎病死率下降至6.1%,远低于全球各国报道的病死率。本文对该指南之诊疗方案进行分析,并与我国现行指南进行对比,以期对AP患者的临床诊治提供指导意义,并期待日后有更多更深入的该领域相关研究。

It is a significant problem that how to reduce the mortality rate of acute pancreatitis．However,under the guidance of the Pancreatitis Bundles from the 2021 Edition of the Japanese Guidelines for Acute Pancreatitis of patients with acute pancreatitis,the overall fatality rate of acute pancreatitis in Japan has decreased to 2.6%,and the fatality rate of severe acute pancreatitis has decreased to 6.1%,which is much lower than the fatality rate reported around the world．We analyze the diagnosis and treatment methods of this guideline and compare it with the current guideline in China,in order to have more relevant studies in the future．

目的 初步探究胆管结扎诱导的梗阻性胆汁淤积对大鼠肝细胞的影响。方法 10只Lewis大鼠随机分为对照组和胆汁淤积组,每组各5只,胆汁淤积组采用胆管结扎2周诱导梗阻性胆汁淤积大鼠模型。苏木精-伊红染色和苯胺蓝染色比较组织病理变化,使用生化分析比较两组小鼠肝功能情况。采用改良的两步胶原酶灌注分离原代肝细胞,通过RT-qPCR检测两组小鼠肝细胞标志基因、细胞增殖标志基因以及胆管细胞标志基因的表达情况。结果 与对照组相比,胆汁淤积组肝脏表现为明显的肝组织紊乱和纤维胶原蛋白沉积以及肝功能的损害。胆汁淤积组较对照组的原代肝细胞更高表达细胞增殖标志基因：细胞增殖标志物（Ki67）基因,叉头盒M1蛋白（Foxm1）基因,增殖细胞核抗原（Pcna）基因和肝细胞生长因子（HGF）基因（P<0.05）;胆汁淤积组的原代肝细胞表达更低水平的肝细胞标志基因：白蛋白（Alb）基因,多药耐药相关蛋白2（Mrp2）基因,胆盐输出泵（Bsep）基因和肝细胞连环蛋白1（Catenin1）基因（P<0.05）,同时表达更高水平的胆管细胞标志基因：细胞角蛋白7（Ck7）基因,细胞角蛋白 19（Ck19）基因,胆管细胞多药耐药性蛋白1（Mdr1）基因和胆管细胞囊性纤维化跨膜传导调节因子（Cftr）基因（P<0.05）以及肝祖细胞标志基因：上皮细胞黏附分子（Epcam）基因和Y染色体性别决定区-盒转录因子9（Sox9）基因（P<0.05）。结论 胆汁淤积可诱导肝细胞向胆管细胞特性转化的可塑性。

Objective To explore the effect of bile duct ligation induced obstructive cholestasis on rat hepatocytes. Methods Ten Lewis rats were randomly divided into control group and cholestasis group, and the cholestasis was induced by bile duct ligation for 2 weeks. The histopathological changes were compared by H&E and aniline blue staining and the liver function was compared by biochemical analysis. Primary hepatocytes were isolated by modified two-step collagenase perfusion, and the expressions of hepatocyte marker genes, cell proliferation marker genes and cholangiocyte marker genes were detected by RT-qPCR. Results Compared with the control group,the liver of the cholestatic group showed obvious disordered histopathology, deposition of fibrous collagen and impaired liver function. Compared with the control group, the primary hepatocytes in the cholestasis group expressed higher cell proliferation-related genes（Ki67,Foxm1,Pcna and HGF）（P<0. 05）. Primary hepatocytes in the cholestasis group expressed lower levels of hepatocyte marker genes（Alb,Mrp2,Bsep and Catenin1）（P<0. 05）,and higher levels of cholangiocyte marker genes（Ck7,Ck19,Mdr1 and Cftr）（P<0. 05）and higher levels of the hepatic progenitor cell marker genes（Epcam and Sox9）（P<0. 05）. Conclusions Cholestasis induces rat hepatocyte plasticity in the transformation into bile duct properties.