不同补肾阴方药对慢性哮喘气道重构的调节作用及其作用机制研究

Antiasthmatic effects of different tonifying kidney-Yin formulas and their effects on airway remodeling in chronic asthma

左归丸、六味地黄丸均含有"三补方"的组分,均对慢性哮喘具有治疗作用。为研究3种补肾阴方剂的抗哮喘作用差异及其分子机制,以卵清白蛋白建立BALB/c小鼠慢性哮喘模型。模型动物分别灌胃给予左归丸、六味地黄丸或三补方。给药后观察抓鼻次数、打喷嚏次数;肺部病理切片测定气道平滑肌厚度、基底膜厚度、胶原沉积面积及杯状细胞数;Western blot,RT-PCR法检测肺组织MMP-9,TGF-β1,Smad2,Smad3,Smad7的表达。结果显示左归丸组抓鼻次数、打喷嚏次数显著低于三补方组,气道重构抑制程度显著高于三补方组;六味地黄丸组抓鼻次数、打喷嚏次数显著低于三补方组,胶原沉积面积及杯状细胞数显著低于三补方组。4种气道重构相关因子中,左归丸组MMP-9,TGF-β1,Smad2,Smad3显著低于三补方组,Smad7显著高于三补方组。六味地黄丸组Smad7显著高于三补方组,MMP-9与模型组及三补方组均无显著差异。提示3种补肾阴药方抗哮喘作用存在显著差异,左归丸对MMP-9的调节作用及六味地黄丸对Smad7的调节作用可能与3种组方对气道重构抑制作用的差异有关。

Both of Zuogui Wan（ZGW） and Liuwei Dihuang Wan（LWDHW） contain ingredients of Sanbufang（SBF）, which have been proven to have antiasthmatic effects.In order to study the antiasthmatic effects of the three tonifying kidney-Yin formulas and their mechanisms, BALB/c mice were randomly divided into 5 groups.Chronic asthma was induced by ovalbumin.Mice in treated groups were respectively given 49.0 g＆#183;kg-1ZGW, 35.0 g＆#183;kg-1LWDHW and 22.4 g＆#183;kg-1SBF by gavage.Those in normal and model group were given normal saline.After treatment, sneeze and nose scratching times of mice were observed.Histological lung sections were prepared to determine the basement membrane thickness（BMT）, smooth muscle thickness（SMT）, collagen area（CA） and numbers of goblet cells（GCN）.Western blotting and RT-PCR were used to determine the expression levels of MMP-9, TGF-β1, Smad2, Smad3 and Smad7.The results showed that sneeze and nose scratching times of ZGW group were significantly lower than those of SBF group.Its inhibition degree on airway remodeling was significantly higher than SBF group.Sneeze and nose scratching times of LWDHW group were significantly lower than SBF group.Its CA and GCN were significantly lower than SBF group.Regarding the four airway remodeling related factors, MMP-9, TGF-β1, Smad2 and Smad3 of ZGW group were significantly lower than those of SBF group, and its Smad7 was significantly higher than SBF.Smad7 of LWDHW group was significantly higher than SBF.There was no significant difference in MMP-9 between model group and SBF group.The results indicate that there are significant differences in the antiasthma effect of these tonifying kidney-Yin formulas.The regulatory effects of ZGW and LWDHW on MMP-9 and Smad7 may be correlated with the differences in the inhibitory effect of airway remodeling of the three formulas.