血管紧张素Ⅱ在大鼠酒精性肝纤维化发病机制中的作用  

Role of angiotens Ⅱ in pathogenesis of alcoholic liver fibrosis in rats

作　　者：于继红[1] 陈玉帅[1] 林红[1] 傅宝玉[1] 

机构地区：[1]中国医科大学附属第一医院消化内科,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2008年第31期3492-3497,共6页World Chinese Journal of Digestology

摘　　要：目的:明确血管紧张素Ⅱ(AngⅡ)在酒精性肝纤维化发生中的作用,为临床治疗提供新的靶点.方法:Wisar大鼠110只随机分为对照组(n=30),酒精组(n=50),Captopril组(n=30);酒精组采用乙醇灌胃法制备酒精性肝病动物模型,Captopril组在乙醇灌胃2wk后,加用Captopril8g/(kg·d),日2次灌胃,同时继续乙醇灌胃,共12wk.应用HE和VG染色观察肝脏病理组织学改变;放射免疫分析法检测血清HA、LN含量以及血浆和肝组织内AngⅡ水平;免疫组织化学染色检测肝组织内Ⅰ、Ⅳ型胶原含量.结果:酒精组血浆AngⅡ水平在8wk后开始升高,12wk时达到顶点,明显高于对照组(1250.50±170.06 vs 598.20±83.73,P<0.0005).实验4,8,12wk,肝组织内AngⅡ进程进行性升高,与对照组相比差异具有统计学意义(1083.4±197.45 vs 568.2±89.82,1382.5±154.88 vs 570.2±77.63,1504.00±173.12 vs 579.2±87.65,均P<0.0005).Captopril组未见明显的肝细胞脂肪变性、坏死及炎性细胞浸润,无纤维条索形成;而这些改变在酒精组均非常明显.12wk末,酒精组血清LN和HA与对照组及Captopril组比较差异具有统计学意义(33.9±2.77 vs 22.0±2.31,24.2±1.9;72.5±3.31 vs 54.4±3.15,56.7±3.22,均P<0.05);Ⅰ、Ⅳ型胶原的定位在两组没有明显差别,但在染色强度及染色面积上,Captopril组明显低于酒精组(6.45±0.41,7.01±0.49 vs 17.23±0.62,18.04±0.89,均P<0.0005).结论:酒精性肝纤维化时血浆及肝组织内AngⅡ增高,血管紧张素转换酶抑制剂Captopril能抑制酒精性肝纤维化的形成.AngⅡ具有促进酒精性肝纤维化发生的作用.AIM： To determine role of angiotensin Ⅱ （Ang Ⅱ） in alcoholic liver fibrosis and to provide a new suitable agent for clinical treatment. METHODS： Wistar male rats were randomly divided into 3 groups： control group （n = 30）, experimental group （n -- 50） which were intragastricaly infused with NS or alcohol, and Captopril group （n = 30） treated with captopril twice a day for 12w [8 g/（kg·d）] following two weeks＇ of alcohol infusion. HE and van Giesion staining were used to observe the histological changes, and serum or hepatic hyaluronic acid, laminin and angiotensin Ⅱ were detected using radio- immunoassay method. Immunohistochemistry staining was used to detect the expressions of type Ⅰ and type Ⅳ collagen in liver. RESULTS： The serum AnglI level began to increase after eight weeks-- of ethanol feeding in alcohol-fed rats and reached the highest level at the end of 12 weeks, significantly higher than controls （1250.50 ± 170.06 vs 598.20 ± 83.73, P 〈 0.0005）. Ang lI, detected in liver, progressing increased and showed significant difference between alcohol-fed rats and controls （1083.4 ± 197.45 vs 568.2 ± 89.82, 1382.5 ± 154.88 vs 570.2 ± 77.63, 1504.00 ± 173.12 vs 579.2 ± 87.65, all P 〈 0.0005）. HE and van Giesion staining showed no degeneration or necrosis or inflammatory cell infiltration or fibroproliferation in captopriltreated rats, whereas dramatic changes were observed in alcohol-fed rats. At the end of week 12, serum hepatic hyaluronic acid and laminin level were significantly increased in alcoholfed rats than either the controls or the captopril- treated rats （33.9 ± 2.77 vs 22.0 ± 2.31, 24.2 ± 1.9; 72.5 ± 3.31 vs 54.4 ± 3.15, 56.7 ± 3.22, all P 〈 0.05）. The result of immunohistochemistry staining showed no different location of positive staining, but the strength and areas of type Ⅰ or type Ⅳ collagen-positive staining were significantly lower in captopril-treated rats than in alcoholfed rats （6.45 ± 0.41, 7.01 ± 0.49 vs 1

关 键 词：血管紧张素Ⅱ 肝纤维化 酒精 大鼠 

分 类 号：R575.2[医药卫生—消化系统]