苇茎汤对慢性阻塞性肺疾病急性加重期模型大鼠的改善作用及机制

Improvement Effects of Weijing Decoction on AECOPD Model Rats and Its Mechanism

目的:研究苇茎汤对慢性阻塞性肺疾病急性加重期(AECOPD)模型大鼠的改善作用及可能机制。方法:将55只雄性SD大鼠按随机数字表法随机分为正常组,模型组,苇茎汤低、高剂量组(8.37、16.74g/kg,以生药量计)和地塞米松组(阳性对照组,0.09mg/kg),每组11只。除正常组外,其余各组大鼠均采用香烟联合脂多糖诱导的方法建立AECOPD模型。造模结束后,正常组和模型组大鼠灌胃水,其余各组大鼠灌胃相应药物,每天灌胃2次,连续14d。末次灌胃后,测定大鼠血清中白细胞介素1β(IL-1β)水平,观察大鼠肺组织和支气管的病理学变化,测定大鼠肺组织中基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)mRNA表达水平及Ras同源基因家族成员A(RhoA)、蓬乱蛋白相关形态形成活化因子1(DAAM1)和细胞增殖抑制基因(HSG)蛋白的表达水平。结果:与正常组比较,模型组大鼠血清中IL-1β水平以及肺组织中MMP-9、TIMP-1mRNA表达水平和RhoA、DAAM1蛋白表达水平均显著升高(P<0.05),肺组织中HSG蛋白表达水平显著降低(P<0.05);支气管周围有较多慢性炎症细胞浸润,部分气道黏膜上皮脱落;肺泡代偿性扩张,肺间隔毛细血管扩张、充血。与模型组比较,苇茎汤高剂量组大鼠血清中IL-1β水平和肺组织中MMP-9、TIMP-1mRNA表达水平均显著降低(P<0.05);苇茎汤低、高剂量组大鼠肺组织中RhoA、DAAM1蛋白表达水平均显著降低(P<0.05),HSG蛋白表达水平均显著升高(P<0.05);苇茎汤高剂量组大鼠支气管周围炎症细胞浸润、气道黏膜脱落等病理形态学变化均得到明显改善,肺泡上皮结构较完整、未见明显肺扩张。结论:苇茎汤对AECOPD模型大鼠具有一定的改善作用;其机制可能与下调肺组织中MMP-9、TIMP-1mRNA和RhoA、DAAM1蛋白的表达,上调肺组织中HSG蛋白的表达,从而抑制气道重建有关。

OBJECTIVE:To study the improvement effects of Weijing deco ction on AECOPD model rats and its possibile mechanism.METHODS:Totally 55 male SD rats were randomly divided into normal group,model group,Weijing decoction low-dose and high-dose groups(8.37,16.74 g/kg,by crude drug),dexamethasone group(positive control group,0.09 mg/kg),with 11 rats in each group.Except for normal group,AECOPD model was induced by cigarettes combined with lipopolysaccharide in other groups.After modeling,normal group and model group were given constant volume of water intragastrically,and other groups were given relevant medicine intragastrocally,twice a day,for 14 days.After last intragastric administration,the serum level of IL-1βwas determined,and pathological changes of lung tissue and bronchus were observed in each group;mRNA expression of MMP-9 and TIMP-1 genes in lung tissue were detected;protein expression of Ras homologous gene family member(RhoA),dishevelled associated activator of morphogenesis-1(DAAM1)and hyperplasic suppress gene(HSG)in lung tissue were also determined.RESULTS:Compared with normal group,the levels of IL-1βin serum,mRNA expression of MMP-9 and TIMP-1 as well as protein expression of RhoA and DAAM 1 in lung tissue were increased significantly in the model group(P<0.05),while protein expression of HSG in lung tissue was decreased significantly(P<0.05);there were many chronic inflammatory cells infiltrating around the bronchus,some airway mucosa epithelium exfoliating,alveolar compensatory dilation,pulmonary septal capillary dilation and hyperemia.Compared with model group,the levels of IL-1βin serum,mRNA expression of MMP-9 and TIMP-1 in lung tissue were decreased significantly in Weijing decoction high-dose group(P<0.05);the protein expression of RhoA and DAAM 1 in lung tissue were decreased significantly in Weijing decoction low-dose and high-dose groups(P<0.05),while the protein expression of HSG in lung tissue was increased(P<0.05);the pathological changes of Weijing decoction high-dose group,such as inflammatory cells infiltrating around the bronchus and shedding of airway mucosa,were improved significantly,and there was complete alveolar epithelium structure but no obvious pulmonary dilation.CONCLUSIONS:Weijing decoction can improve AECOPD model rats to certain extent;its mechanism may be associated with down-regulating mRNA expression of MMP-9 and TIMP-1 as well as protein expression of RhoA and DAAM 1 in lung tissue,up-regulating protein expression of HSG in lung tissue so as to inhibit the airway remodeling.