丹酚酸B、甘草次酸、白藜芦醇单用及联用对小鼠肺间质纤维化影响的实验研究

Single or Combining Use of Salvianolic Acid B,Glycyrrhetinic Acid and Resveratrol on Pulmonary Fibrosis Mice Induced by Bleomycin

目的:探究丹酚酸B(Sal B)与甘草次酸(GA)、白藜芦醇(RES)单用及合用对博来霉素诱导肺纤维化小鼠的干预作用。方法:采用气管注射博来霉素(BLM)的方法复制小鼠肺纤维化模型,设置对照组、模型组、醋酸地塞米松组(DXM)组、甘草次酸(GA)组、白藜芦醇(RES)组、丹酚酸B(Sal B)组、GA+RES组、GA+Sal B组、RES+Sal B组、GA+RES+Sal B组,共10组,7 d后开始口服给药治疗,记录小鼠日常情况、体重,于造模后7、14、28 d分别采集小鼠肺部样本,计算肺系数及检测肺组织羟脯氨酸(Hyp)含量。结果:7 d各BLM造模小鼠体重均小于对照组,14 d、28 d各给药组小鼠体重小于对照组且大于模型组;14 d各给药组肺系数明显小于模型组,大于对照组,28 d除RES组外,其余各给药组肺系数均小于模型组;7 d模型组肺组织Hyp含量小于对照组,无显著性差异(P>0.05),14 d、28 d各组Hyp含量不同程度变大,各给药组Hyp含量小于模型组大于对照组,28 d时,DXM组Hyp含量小于模型组且差异有统计学意义(P_(DXM)=0.012 7)。除GA+Sal B组和三药合用组外其余组与DXM组差异有统计学意义。两两合用给药组及三药合用给药组Hyp略小于单用给药组,差异无统计学意义。结论:GA、Sal B、RES单用及合用均对BLM致小鼠肺纤维化显示出一定的干预作用,两两合用给药、三药合用干预效果略好于单味给药,其中两两合用给药组中,Sal B与GA配伍效果相对较好,三味药合用对肺纤维化前期炎症细胞产生阶段影响较大。

Objective： To study the therapeutic effect of single or combining use of Salvianolic acid B（ Sal B）,Glycyrrhetinic acid（ GA） and Resveratrol（ RES） on Bleomycin- induced pulmonary fibrosis mice. Methods： Animals were randomly divided into control group,model group,DXM group,GA group,RES group,Sal B group,GA ＋ RES group,GA ＋Sal B group,RES ＋ Sal B group and GA ＋ RES ＋ Sal B group. Except the control group,animal model groups（ the model group and the drug deliver groups） were established by intratracheal injection of bleomycin（ BLM） and oral administration was given after replicated for 7 d. The body weight,the lung index and level of hydroxyproline（ Hyp） in lung tissue were measured to observe the effect of drug on 7 d,14 d and 28 d. Results： The weights of model group were less than that of control group on 7 d and showed a significant difference（ P〈0. 05）. The weights of administration groups were less than that of control group and higher than that of the model group on 14 d and 28 d. The lung index of administration groups was lower than that of the model group significantly（ P = 0. 003） on 7 d. The levels of Hyp in lung of drug treatment groups were less than those of the model group on 14 d and 28 d. Combining use was slightly better than single use.GA ＋ RES group,GA ＋ Sal B group and GA ＋ RES ＋ Sal B group were better than single drug delivery group. Conclusion：The two drug combination has a better effect on Bleomycin- induced pulmonary fibrosis mice than single drug delivery,but there was no significant difference. The three drug combination groups were slightly better than single drug delivery but had no advantage.