氧化苦参碱抗肝纤维化作用的病理学研究  

Experimental study of the inhibitory effect of oxymatrine on hepatic fibrosis induced by CCl_4

作　　者：余小虎[1] 朱金水[1] 朱祖明[1] 俞华芳[1] 朱励[1] 沈波[1] 

机构地区：[1]上海交通大学附属第六人民医院消化科,上海200233

出　　处：《胃肠病学和肝病学杂志》2004年第5期485-487,共3页Chinese Journal of Gastroenterology and Hepatology

基　　金：上海市医学发展基金重点研究课题 (99ZD0 0 1 )

摘　　要：目的　研究氧化苦参碱对实验性大鼠肝纤维化的治疗作用 ,并探讨其作用机理。方法　 80只Wistar大鼠 ,随机挑选72只给予皮下注射 5 0 %四氯化碳及以 10 %酒精替代饮用水 ,其余 8只作为正常对照组 (N组 ) ,8周后造模组中随机处死 16只 (M组 )证实肝纤维化形成 ,剩下肝纤维化大鼠随机分成二组 ,分别给予氧化苦参碱腹腔注射 (T组 ,10 0mg·kg-1·d-1)和生理盐水腹腔注射 (R组 ,10mg·kg-1·d-1) ,疗程为 9周 ,实验结束时全部大鼠采血后处死 ,分别行HE染色评估肝纤维化程度 (采用纤维化半定量计分系统 ,SSS)、免疫组化法检测肝组织中TGFβ1水平、Masson染色法评估肝组织中胶原纤维百分比。 结果　氧化苦参碱组 (T组 )大鼠肝纤维化程度较自然恢复组 (R组 )明显减轻 ( 7.5 4± 2 .2vs10 .44± 3 .0 ,P <0 .0 5 ) ,两组大鼠肝组织中胶原面积密度差异显著( 10 .4± 3 .0vs 16.8± 3 .5 ,P <0 .0 5 ) ;T组血清转氨酶显著高于R组 (P <0 .0 5 ) ,M组大鼠肝组织TGFβ1的表达较N组明显升高( 12 5 .2± 2 2 .7vs 3 0 .5± 9.5 ,P <0 .0 1) ,氧化苦参碱治疗后肝组织TGFβ1明显减少 (P <0 .0 1)。 结论　氧化苦参碱具有明显的逆转肝纤维化作用 。Objective To investigate the therapeutic effects and mechanism of oxymatrine on experimental hepatic fibrosis in rats. Methods Hepatic fibrosis was induced in 72 Wistar rats within 8 weeks using subcutaneous injection of carbon tetrachloride (twice a week, 3ml·kg-1) together with feeding with alcohol (containing 10% ethanol) and another 8 rats were routinely fed as normal group(N group), 16 rats were sacrificed to ensure the onset of hepatic fibrosis(M group), then all the rest rats with hepatic fibrosis were randomly divided into two groups receiving intraperitoneal injection of oxymatrine ( 100 mg·kg·d^(-1), T group)and normal saline(10 mg·kg·d^(-1), R group) respectively for consecutive 9 weeks, the stage of hepatic fibrosis was assessed through HE staining and observed under light microscope( semi-quantitative scaling system, SSS).The area density of collagen in liver speciments was assessed through Masson staining and observed under light microscope; transforming growth factor beta 1 (TGF beta 1) were determined with immunohistochemistry assay. Results The stage of hepatic fibrosis in T group was obviously reduced when compared to R group(7.5±2.2 vs 10.4±3.0, P<0.05);the differences of serum transaminases between the two groups were also significant(P<0.05);the area density of collagen in liver tissues was obviously lower in T group than that in M group(10.4±3.0 vs 22.5±4.8, P<0.01), what's more, the difference was also significant when compared to R group (10.4±3.0 vs 16.8±3.5, P<0.05).Imaging analysis revealed that TGFbeta 1 immunohistological staining areas were markedly shrinked in oxymatrine treated group(T group) compared with M group and R group(P<0.01).Conclusion Oxymatrine has obvious therapeutic effects on rats with hepatic fibrosis. The mechanism may be correlated to the reduction of TGF beta 1.

关 键 词：氧化苦参碱 肝组织 鼠肝 大鼠 抗肝纤维化作用 病理学研究 β1 表达 染色法 水平 

分 类 号：R575.2[医药卫生—消化系统] R512[医药卫生—内科学]