四氯化碳、酒精与四氯化碳联合、胆管结扎致SD大鼠肝纤维化病理学比较

Pathology Comparison of Hepatic Fibrosis SD Rat Caused by Carbon Tetrachloride,Alcohol and Carbon Tetrachloride Combination and Bile Duct Ligation

目的研究四氯化碳、酒精与四氯化碳联合、胆管结扎致SD大鼠肝纤维化模型肝脏的病理学改变,初步探讨肝纤维化发病机制。方法四氯化碳组SD大鼠以3 mg/kg的剂量(首次剂量加倍)皮下注射50%四氯化碳(四氯化碳∶橄榄油=1∶1),每周2次,连续注射6周;酒精与四氯化碳联合组SD大鼠每日按照10 mL/kg剂量灌服酒精混合物(酒精∶吡唑∶玉米油=10 mL∶25 mg∶2 mL),同时每周2次按0.3 mL/kg剂量给予腹腔注射四氯化碳∶橄榄油(1∶3),连续造模60 d;胆管结扎组大鼠按10 mg/kg体重腹腔注射3%戊巴比妥钠麻醉,腹部皮肤消毒,无菌操作沿腹部正中线剪开腹腔,分离出胆管,在胆管近端和远端2处结扎胆管,28 d后结束实验。试验结束后麻醉动物,解剖取动物肝脏组织,用10%福尔马林固定,进行病理学检查。结果四氯化碳致SD大鼠肝纤维化模型表现为弥漫性脂肪肝、肝炎、肝纤维化;酒精与四氯化碳联合致SD大鼠肝纤维化模型表现为酒精性脂肪肝、肝炎、肝纤维化;胆管结扎致SD大鼠肝纤维化模型表现为胆管增生、肝炎、肝纤维化。结论这3种方法都可以引起大鼠肝脏发生纤维化,其中胆管结扎致SD大鼠肝纤维化造模方法适合于临床胆汁淤积所致肝纤维化的模型建立,其它两种方法适合于化学性、病毒性肝炎引起的肝纤维化模型的建立,可根据不同的实验目的选择不同的方法构建相应的动物模型。

Objective To study the hepatic pathological changes in SD rat hepatic fibrosis model caused by carbon tetrachloride（CTC）,alcohol combined with CTC,bile duct ligation,and discuss the pathogenesis of hepatic fibrosis preliminarily.Methods SD rats in carbon tetrachloromethane group were injected 50% carbon tetrachloromethane（CTC∶Olive oil=1∶1） hypodermically with dosage of 3 mg/kg（first dose doubled）,2 times every week,for 6 weeks continuously.SD rats in alcohol combined with CTC group were drenched daily by alcohol mixture（alcohol∶pyrazole∶corn oil=10 mL∶25 mg∶2 mL） with dosage of 10 mL/kg,at the same time,intraperitoneal injected with dosage of 3 mg/kg CTC∶Olive oil（1∶3） 2 times every week,for 6 weeks continuously.SD rats in bile duct ligation group were anesthetized by 3% pentobarbital sodium intraperitoneal injection with dosage of 10mg/kg body weigh,disinfected abdominal skin,cutted along the abdomen to separate the bile duct and ligate bile duct at the proximal and distal bile duct with aseptic technique,28 days later ended the experiment.After the test,we anesthetized SD rats,dissected liver tissues with 10% formalin fixed for pathological inspection.Conclusions SD rat hepatic fibrosis model induced by CTC characterized by diffuse fatty liver,hepatitis and hepatic fibrosis;SD rat hepatic fibrosis model induced by alcohol combined with CTC characterized by alcoholic fatty liver,hepatitis and hepatic fibrosis;SD rat hepatic fibrosis model induced by bile duct ligation characterized by bile duct hyperplasia,hepatitis and hepatic fibrosis.Result These three methods can cause hepatic fibrosis occurs,in which the method for SD rat hepatic fibrosis model caused by CTC is suitable for clinical cholestasis induced hepatic fibrosis model to establish,the other two methods are suitable for chemical,viral hepatitis induced hepatic fibrosis model to establish,we can choose different method to establish corresponding animal model according to different experiment purpose.