小檗碱联合吡喹酮对大鼠日本血吸虫病肝纤维化组织MMP-13与TIMP-1表达的影响  

Effects of Berberine Combined with Praziquantel on the Expression of MMP-13 and TIMP-1 in the Liver Fibrosis Tissue of Schistosoma japonicum Infected Rats

作　　者：骆中华[1] 吕飞[1] 

机构地区：[1]华中科技大学同济医学院附属普爱医院消化科,武汉430035

出　　处：《医药导报》2016年第1期39-43,共5页Herald of Medicine

摘　　要：目的探讨小檗碱联合吡喹酮对血吸虫病大鼠肝纤维化的作用及其机制。方法感染日本血吸虫尾蚴后的大鼠80只,随机均分为4组(n=20)。模型对照组不作任何治疗;吡喹酮组在感染血吸虫尾蚴6周时给予吡喹酮500 mg·kg-1·d-1灌胃2 d;小檗碱组在感染血吸虫尾蚴6周时予小檗碱150 mg·kg-1·d-1灌胃6周;吡喹酮联合小檗碱组在感染血吸虫尾蚴6周时予吡喹酮500 mg·kg-1·d-1灌胃2 d后,继以小檗碱150 mg·kg-1·d-1灌胃6周。另取10只正常大鼠作为正常对照组。灌胃6周末检测各组大鼠肝组织丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-Px)活性及基质金属蛋白酶(MMP)-13、基质金属蛋白酶抑制剂(TIMP)-1、Ⅰ型胶原、Ⅲ型胶原的表达变化。结果与模型对照组比较,吡喹酮组、小檗碱组中肝组织MDA含量、TIMP-1、Ⅰ型胶原、Ⅲ型胶原表达水平明显下降(P<0.05),GSH-Px活性、MMP-13表达及MMP-13/TIMP-1比值明显升高(P<0.05)。吡喹酮组和小檗碱组差异无统计学意义(均P>0.05)。吡喹酮联合小檗碱组肝组织中MDA含量、TIMP-1、Ⅰ型胶原、Ⅲ型胶原表达水平分别为(2.215±1.316)nmol·mg-1,0.642±0.052,0.273±0.102,0.203±0.104,与吡喹酮组、小檗碱组比较,均明显下降(P<0.05);GSH-Px活性、MMP-13表达及MMP-13/TIMP-1比值分别为(21.89±1.54)n U·mg-1,0.588±0.027,0.726±0.138,与吡喹酮组、小檗碱组比较,均明显升高(P<0.05)。结论小檗碱可通过降低肝组织氧化应激水平,减轻MMP-13/TIMP-1表达比值失衡而抑制血吸虫肝纤维化,可与吡喹酮联用发挥协同、增效作用。Objective To study the effect and mechanismof berberine combined with praziquantel on the liver fibrosis of Schistosoma japonicum infected rats. Methods Eighty rats infected with Schistosoma japonicum were randomly divided into four groups（ n = 20）. The model control group was untreated. The rats in praziquantel group were treated with praziquantel500 mg·kg^-1·d^-1by intragastric administration for 2 days,those in the berberine group were i. g. treated with berberine150 mg·kg^-1·d^-1for six weeks. The rats in berberine combined with praziquantel group were treated with berberine150 mg·kg^-1·d^-1for six weeks following praziquantel 500 mg·kg^-1·d^-1i.g. for 2 days.By the 6th week after administration,the content of MDA,the activity of GSH-Px and the expressions of MMP-13,TIMP-1,typeⅠ and type Ⅲ collagen in liver tissue of mice were detected. Results Compared with the model control group,the content of MDA and the expressions of TIMP-1,typeⅠ and type Ⅲ collagen in liver tissue were decreased obviously（ P 〈0. 05） and the activity of GSH-Px,the expression of MMP-13 and the ratio of MMP-13 / TIMP-1 were increased obviously（ P 〈0. 05） in both praziquantel and berberine groups,but there was no significant difference between these 2 groups（ P0.05）.The content of MDA（ 2.215± 1.316 nmol·mg^-1）,TIMP-1expressions（ 0.642±0.052）,and typeⅠ（ 0.273±0.102） type Ⅲ（ 0.203±0.104） collagenin liver tissue were decreased obviously（ P〈0.05）.GSH-Px（ 21.89±1.54） n U·mg^-1,MMP-13（ 0.588±0.027） and the ratio of MMP-13/TIMP-1（ 0.726±0.138） were increased markedly（ P〈0.05） in the combination group compared with the monotherapy. Conclusion Berberine may inhibit hepatic fibrosis by Schistosoma japonicum infection via reducing the level of oxidative stress and imbalance of expression ratio of MMP-13 / TIMP-1,which may play a synergistic effect with praziquantel.

关 键 词：小檗碱 吡喹酮 纤维化 肝 血吸虫病 氧化应激 基质金属蛋白酶 

分 类 号：R975.5[医药卫生—药品] R965[医药卫生—药学]