慢性肝病不同肝纤维化阶段的肝脏体积及其病理变化特点  

Characteristics of liver volume and pathological changes with different stages of liver fibrosis in chronic liver disease

作　　者：朱亭亭 李正鑫 袁杰[5] 黄恺 陈高峰 国荣芳 赵志敏 刘成海 Zhu Tingting;Li Zhengxin;Yuan Jie;Huang Kai;Chen Gaofeng;Guo Rongfang;Zhao Zhimin;Liu Chenghai(Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases,Ministry of Education,Shanghai 201203,China;Gongli Hospital of Shanghai Pudong New Area,Shanghai 200120,China;Departments of Radiology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肝病研究所,上海201203 [2]上海市中医临床重点实验室,上海201203 [3]肝肾疾病病证教育部重点实验室,上海201203 [4]上海市浦东新区公利医院,上海200130 [5]上海中医药大学附属曙光医院影像医学科,上海201203

出　　处：《中华肝脏病杂志》2024年第6期517-524,共8页Chinese Journal of Hepatology

基　　金：国家自然科学基金面上项目(82274305);上海市临床重点专科建设项目(shslczdzk01201);"十三五"国家科技重大专项项目(2018ZX10302204);上海市促进市级医院临床技能与临床创新能力三年行动计划项目·重大疾病临床技能提升项目(16CR1026B)。

摘　　要：目的:测量不同肝纤维化程度慢性肝病患者的肝脏整体与分叶体积,并观察患者肝脏微血管、肝细胞消亡与再生等病理改变,以期了解肝纤维化时肝脏宏观体积变化及其与肝组织微观病理的联系。方法:收集同时进行肝活检组织和腹部磁共振成像检查的慢性乙型肝炎、酒精性脂肪肝、自身免疫性肝病、非酒精性脂肪性肝病、药物性肝病的慢性肝病患者53例。采用Masson染色并根据Ishak肝纤维化分期,将患者分为肝纤维化早期(F1~2)、中期(F3~4)和晚期(F5~6)。应用ITK-SNAP软件测量肝脏和脾脏体积。通过CD31免疫组织化学染色反映肝内血管生成,Ki67与肝细胞核因子4α多重荧光免疫组织化学染色反映肝细胞再生,谷氨酰胺合成酶(GS)染色判断肝实质细胞消亡,原位末端标记法观察肝细胞凋亡。Spearman相关性分析肝体积变化与肝组织病理变化之间的关系。结果:随着肝纤维化进展,总肝体积和右肝叶体积逐渐降低(P<0.05),脾脏体积逐渐升高(P<0.05),CD31、GS的表达逐渐增加(P<0.05),Ki67的表达先升高后下降(P<0.05)。CD31阳性率与右肝叶体积(r=-0.609,P<0.001)和总肝体积(r=﹣0.363,P=0.017)呈负相关。Ki67阳性率与右肝叶体积呈正相关(r=0.423,P=0.018),凋亡细胞的阳性率与总肝体积呈显著负相关(r=-0.860,P<0.001)。GS阳性率与右肝叶体积呈负相关(r=﹣0.440,P=0.002),肝细胞消亡数量与右肝叶体积呈负相关(r=﹣0.476,P=0.013)。CD31阳性染色面积与Ki67阳性染色面积呈负相关(r=﹣0.511,P=0.009)。结论:随肝纤维化进展,患者总肝体积与右肝叶体积缩小,主要与肝组织中肝细胞减少与微血管紊乱有关。Objective To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature,hepatocyte apoptosis,and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease.Methods 53 patients with chronic hepatitis B,alcoholic fatty liver disease,autoimmune liver disease,nonalcoholic fatty liver disease,and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected.Patients were divided into early(F1-2),middle(F3-4),and late(F5-6)in accordance with the Ishak fibrosis stage and Masson stain.The liver and spleen volumes were measured using ITK-SNAP software.CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis.Ki67 and HNF-4αmultiplex immunohistochemical staining were used to reflect hepatocyte regeneration.GS staining was used to determine parenchymal extinction lesions.TUNEL staining was used to observe hepatocyte apoptosis.Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes.Results As liver fibrosis progressed,the total liver volume and right lobe liver volume gradually decreased(P<0.05),while the spleen volume gradually increased(P<0.05).The expression of CD31 and GS gradually increased(P<0.05),and the expression of Ki67 first increased and then decreased(P<0.05).The positivity rate of CD31 was negatively correlated with the right lobe liver volume(r=-0.609,P<0.001)and the total liver volume(r=-0.363,P=0.017).The positivity rate of Ki67 was positively correlated with the right lobe liver volume(r=0.423,P=0.018),while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume(r=-0.860,P<0.001).The positivity rate of GS was negatively correlated with the rig

关 键 词：肝纤维化 肝体积 肝细胞消亡 肝再生 肝细胞血管生成 诊断 

分 类 号：R575[医药卫生—消化系统]