茅台酒诱导金属硫蛋白的作用及其对肝星状细胞的影响  

Effect of Maotai liquor in inducingmetallothioneins and on hepaticstellate cells

作　　者：程明亮[1] 吴君[1] 王海琴[1] 徐列明[2] 谭英姿[2] 刘平[2] 李诚秀[3] 黄能慧[3] 姚玉梅[1] 任兰振[3] 叶兰[3] 李铃[3] 贾美琳[3] 

机构地区：[1]贵阳医学院传染病教研室,贵州省贵阳市550004 [2]上海中医药大学,上海市200020 [3]贵阳医学院药理教研室,贵州省贵阳市550004

出　　处：《世界华人消化杂志》2001年第12期1369-1373,共5页World Chinese Journal of Digestology

基　　金：贵州省科学技术重点项目;黔科合计字;No.19992015

摘　　要：目的探讨饮用贵州茅台酒(下称茅台酒)不发生肝纤维化的可能机制。方法 SD大鼠用茅台酒灌胃连续56d,断头取血测生化指标,剖服取肝称重计算肝系数及测肝组织金属硫蛋白;鼠分离培养肝星状细胞及对人体肝星状细胞作用,观察肝星状细胞增殖和胶原生成的情况。结果茅台酒组与正常对照组相比,大鼠肝脏MT含量分别为 216.0ng.g^(-1)±10.8ng.g^(-1)和10.0ng.g^(-1)±2.8ng.g^(-1),茅台酒组明显增加(P<0.05).经茅台酒诱导的动物CCL_4中毒与对照动物CCL_4中毒相比,肝脏MT含量分别为304.8ng.g^(-1)±12.1ng.g^(-1)和126.4ng.g^(-1)±4.8ng.g^(-1),茅台酒组明显增加(P<0.05);MDA含量分别为102.0nmol.g^(-1)±3.4nmol.g^(-1)和150.8nmol.g(^-1)±6.7nmol.g^(-1),茅台酒组明显降低(P<0.05).两组动物CCL_4中毒时肝MT与MDA含量呈显著负相关关系(r=-0.8023,n=20,P<0.01).茅台酒浓度为0,10,50,100,200g.L^(-1)增殖HSC的各管570nmA值分别为0.818,0.742,0.736,0.72,0.682,0.604.自10g.L^(-1)浓度起,茅台酒对肝星状细殖有明显抑制作用,且抑制作用呈浓度依赖性增强(P<0.05,P<0.01).茅台酒浓度为0,10,50,100,200g.L^(-1)增殖HSC细胞层中蛋白Ⅰ型胶原含量分别为61.4,59.9,49.2,50.1,48.7,34.4μg.g^(-1),100～200g.L^(-1)浓度的茅台酒对细胞Ⅰ型胶原分泌有明显抑制作(P<0.05).将其中茅台酒浓度0,50,100g.L^(-1)组细胞进行基因表达分析,计算机图象分析β-actin(n=3)基因表达的灰度值分别为0.88,0.74,0.59,100g.L^(-1)浓度的茅台酒能明显抑制Ⅰ型前胶原基因表达(P<0.05),而50g.L^(-1)低浓度组作用不明显(P>0.05).10g.L^(-1)浓度茅台酒组与10g.L^(-1)浓度酒精组相比,对体外培养人肝细胞的生长的抑制率分别为16.4±2.3和-8.4±2.3,茅台酒组明显增高(P<0.05).结论茅台酒诱导肝脏金属硫蛋白含量增加,从多环节抑制易状细胞的活化及其胶原蛋白生成可能是干预肝纤维化形成的重要机制。AIM To explore the mechanism of preventing hepatic fibrosis by drinking Maotai liquor. METHODS After ingested with Maotai for 56 days consecutively, the male SD rats were decollated for detecting the biological indicators, and the liver was harvested to obtein the hepatic indexes and the level of hepatic metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen production were observed. RFSULTS Hepatic MT contents were 216. 0ng.g^(-1)±10. 8ng.g^(-1) in the rats of Maotai group and 10.0ng.g^(-1)±2.8ng. g^(-1) in the normal control group, which was increased obviously in Maotain group (p<0.05). In the rats with CCL_2 poisoning induced by Maotai, hepatic MT content was 304.8ng.g^(-1)±12. 1ng.g^(-1) whereas in the controls with CCL_4 poisoning, it was 126.4ng.g^(-1)±4.8ng.g^(-1) (p<0.05). MDA was 102.0nmol.g^(-1)±3.4nmol.g^(-1) in Maotai group and 150.8nmol.g^(-1)±6.7nmol.g^(-1) in the control group (p<0. 05). When both the groups were suffering from CCL_4 poisoning, hepatic MT and MDA contents were negatively correlated (r=-0.8023, n=20, p<0.01) The 570nmA values of each tube with HSC regeneration were 0.818, 0. 742, 0.736, 0.72, 0.682, and 0.604 respectively, at Maotai concentrations of 0, 10, 50, 100, and 200g.L^(-1). Starting from 10g.L^(-1), Maotai began to demonstrate obvious inhibitory effects against HSC, and the inhibition was concentratior-dependent (p<0.05, p<0.01). Type I collagen contents in HSC were 61.4, 59.9, 50.1, 49.2, 48. 7, 34.4μg.g^(-1) at Maotai concentrations of 0, 10, 50, 100, and 200g.L^(-1). Maotai at the concentration 100～200g.L^(-1) had obvious inhibitory effect against the secretion of type I collagen (p<0. 05 ). Gene expression analysis was conducted on cells with Maotai concentrations at 0, 50, 100g.L^(-1) respectively and the ash values of β-actin gene expression were 0.88, 0.74, and 0.59 by computer tomographic analysis, suggesting that Maotai at the concentration of 100 g.L^(-1) could obviously inhibit gene expression of type I procollagen(p<0.05), but

关 键 词：芭台酒 金属硫蛋白 诱导 肝星状细胞 

分 类 号：R575.2[医药卫生—消化系统]