醛固酮受体拮抗剂联合甘草酸二铵对大鼠肝纤维化进程的影响

The influence and clinic significance of aldosterone acceptor antagon associate with diammonium glycyrrhizinate on the proceeding of rat hepatic fibrosis

目的:利用醛固酮受体拮抗剂联合甘草酸二铵干预肝纤维化大鼠并检测血清中透明质酸(hyaluronic acid,HA)和血管紧张素1-7(angiotensin(1-7),Ang(1-7))的变化,探讨联合用药对大鼠肝纤维化进程的影响。方法:40只健康雄性SD大鼠用完全随机的方法,随机分成5组:正常对照组、模型组、螺内酯+甘草酸二铵联合治疗组、甘草酸二铵治疗组、螺内酯治疗组。于20、40、60d分别取血,并于60d处死全部SD大鼠,取肝组织做切片处理,HE染色,镜下观察比较各组大鼠肝脏组织结构变化。采用ELISA法测定各组大鼠大鼠血清HA和Ang(1-7)水平的变化。采用SPSS17.0软件进行统计学分析,计量资料用均数±标准差(x珋±s)表示。组间比较釆用单因素方差分析(One-way ANOVA)进行统计分析,多重比较采用LSD-t检验(方差齐),或釆用Dunnett-t检验(方差不齐),P<0.05为有统计学意义。结果:与正常对照组比较,20、40、60d各组HA及Ang(1-7)水平均升高(P<0.05),且呈逐渐升高趋势,而与模型组比较,药物治疗组HA水平降低(P<0.05),但Ang(1-7)水平升高(P<0.05),联合治疗组HA水平更低、Ang(1-7)水平更高。甘草酸二铵治疗组和螺内酯治疗组组间比较无明显差异(P>0.05)。结论:醛固酮受体拮抗剂联合甘草酸二铵对大鼠肝纤维化进程有治疗作用,随肝纤维化进展,血清Ang(1-7)水平升高,且药物治疗后其水平升高更明显,提示Ang(1-7)参与肝纤维化发生发展过程。

Objective： To intervene rat hepatic fibrosis with aldosterone acceptor antagon association with diammonium glycyrrhizinate; and to detect the changes of hyaluronic acid（ HA） and angiotensin（ 1- 7）（ Ang（ 1-7）） level in serum,so as to probe the influence and likely mechanism of treating with association medicine on rat hepatic fibrosis. Methods： 40 male healthy Sprague – Dawley（ SD） rats were randomly divided into five groups：control group,hepatic fibrosis model group,association treatment group,diammonium glycyrrhizinate treat group,spironolactone treat group. Their blood were taken separately in the 20 th,40th and 60 th days. After the 60 th day,all SD rats were sacrificed. The liver tissue of all rats were taken,and then made paraffin section and HE staining.The changing differences of the rats＇ liver tissue in each group were observed by microscope and compared. The serum HA and Ang（ 1- 7） levels were tested by ELISA. All statistical analysis were performed with SPSS17. 0,and shown by mean ± standard（ x^-± s）. The intergroup comparison were taken by One- way ANOVA. Multiple comparison were taken by LSD- t test or Dunnett – t test. It is considered statistical significance when P is less than 0. 05. Results： Compared with the normal control group,the HA and Ang（ 1- 7） levels in each group are step up in the 20 th,40th and the 60 th days,and has the gradually step up tendency. While compared with the model group,the HA level in the drug treatment groups were decreased（ P〈0. 05）,but the Ang（ 1- 7） levels were increased（ P〈0. 05）. In association treatment group,there are less levels of HA,and higher Ang（ 1- 7）levels. The comparasion between diammonium glycyrrhizinate treat group and spironolactone treat group has no significant difference. Conclusion： Aldosterone acceptor antagon associate with diammonium glycyrrhizinate can daly the proceeding of rat hepatic fibrosis. As the development of hepatic fibrosis,the serum Ang（ 1- 7） levels increase,and after the drug treatment the increasing is more significant,which suggests that Ang（ 1- 7） is involed in the development of rat hepatic fibrosis,and it may be a protective indel during liver fibrosis.