高脂高糖、饮酒建立家兔脂肪肝模型及超声量化诊断

目的:模拟人类不良饮食结构建立家兔不同程度脂肪肝模型,进行肝脏背向散射积分 (integrated backscatter,IBS)和图像灰阶平均强度(gray scale,GS)测定,并结合临床研究,探讨具有病理基础的脂肪肝无创性超声量化诊断标准．方法:选用纯种新西兰家兔40只,采用高脂高糖饲料及乙醇饮料建立不同程度脂肪肝模型三组(每组n=10),设立对照组(n=10):临床病例同步进行肝组织病理学及超声检测．病理组织学检测采用苏丹Ⅳ,HE和Masson三色染色:应用HP Sonos 5500超声诊断仪实时检测肝脏IBS,包括图像平均强度(average image intensity,AII)、峰-峰强度及图像强度标准差; 采用Photo shop 7．0直方图分析超声图像GS．所得数据采用SAS8．2进行统计学分析．结果:肝脏AII随脂肪变加重呈递增趋势,正常肝<轻度脂肪肝<中度脂肪肝<重度脂肪肝,尤以近区各组间差异显著(P<0．0001);同等程度肝脂肪变AII随炎症的发生而增大．临床研究显示,IBS对脂肪肝诊断率及与病理组织学符合率(85．7％)较常规超声检测(57．1％) 明显增高,重度脂肪肝AII显著高于轻度脂肪肝(P<0．0001,0．001或0．05)．肝脏GS与AII相关,于肝左、右叶近区二者随病变加重呈一致性增高趋势(r1=0．442 21,P1=0．0012:r2= 0．335 73,P2=0．0160)．中重度脂肪肝伴炎症 GS显著高于正常肝及轻度脂肪肝(P<0．05)．结论:高营养及乙醇联合喂养家兔可快速建立不同程度脂肪性肝病模型;肝脏超声IBS及 GS强度可反映肝脂肪变、炎症和纤维化的病变程度,为脂肪肝无创性量化诊断提供可靠依据．

Establishment of experimental hepatic steatosis model in rabbits and non-invasive quantitative ultrasonic diagnosis of fatty liver disease

AIM: To explore the non-invasive, quantitative ultrasonic diagnostic criteria of fatty liver diseases by establishing a rabbit model of hepatic steatosis and measuring ultrasonic integrated backscatter (IBS) and gray scale (GS). METHODS: Forty healthy New Zealand rabbits were randomly divided into normal control and three experimental groups. Hepatic steatosis was induced by high fat and sugar diet plus drinking water containing five percent of ethanol. Seven patients with mild or severe hepatic steatosis were also recruited in the study. The steatosis, inflammation, and fibrosis of the rabbits' and patients' liver were evaluated by several histo-logical staining methods including Sudan IV, H&E, and Masson's Trichrome staining. Hepatic steatosis was graded as simple steatosis, steato-hepatitis, fibrosis and cirrhosis. Liver IBS including average image intensity (AII) and peak-peak intensity, and GS were measured using HP So-nos 5500 image system. The data were analyzed with one-way ANOVA. RESULTS: Hepatic AII was associated with the aggravated hepatic steatosis in near areas of the rabbit liver, i.e., normal control < mild fatty liver < moderate fatty liver < severe fatty liver (P < 0.0001). Significant differences were observed between AII of steatohepatitis and simple hepatic steatosis. In the patients, IBS was more accurate in the reflection the severity of the liver pathology than routine ultrasonic examination (85.7% vs 57.1%, P < 0.05), and significant differences of AII were observed between mild and severe hepatic steatosis (P < 0.0001, 0.001 or 0.05). The liver GS were markedly increased in the moderate and severe fatty liver as compared with that in normal control and mild fatty liver. Correlation analysis showed that GS and AII were consistently increased as the disease aggravated in the near area of the left and right liver lobes of the animals (r1 = 0.442 21, P1 = 0.0012; r2 = 0.335 73, P2= 0.0160). CONCLUSION: Rabbit fatty liver models can be developed in a short time by high fat and sugar diet plus alcohol. Hepatic IBS and GS intensity can reflect the grades of hepatic steatosis, inflammation and fibrosis, so they may serve as reliable non-invasive tools for the quantitative diagnosis of fatty liver disease.