补肾活血化痰方对COPD大鼠Wnt/β-catenin信号通路及气道重塑的影响  

Effects of decoction for tonifying the kidney,activating blood circulation and resolving phlegm on Wnt/β-catenin signaling pathway and airway remodeling in rats with COPD

作　　者：左然芹 朱慧志[2] 刘向国[1] 任冯春 徐晴雯 ZUO Ranqin;ZHU Huizhi;LIU Xiangguo;REN Fengchun;XU Qingwen(Anhui University of Traditional Chinese Medicine,Hefei 230038,Anhui,China;The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230031,Anhui,China)

机构地区：[1]安徽中医药大学,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《现代中西医结合杂志》2022年第23期3232-3237,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家重点研发计划中医药现代化研究重点专项(2018YFC1704804);安徽省第六批特支计划(dlPtzjh20200050)。

摘　　要：目的观察补肾活血化痰方对慢性阻塞性肺疾病(COPD)大鼠Wnt/β-catenin信号通路及气道重塑的影响。方法将48只雄性SD大鼠随机分为正常组、模型组、桂龙咳喘宁组及阳和平喘颗粒低、中、高剂量组,每组8只。除正常组外,其余组大鼠采用烟熏加气管内滴入脂多糖方法建立COPD模型。造模成功后,桂龙咳喘宁组给予桂龙咳喘宁3.5 mL/100 g灌胃,平喘颗粒低、中、高剂量组分别给予阳和平喘颗粒1.75 g/(kg·d)、3.5 g/(kg·d)、7 g/(kg·d)灌胃,正常组和模型组给予生理盐水灌胃,均连续12周。HE染色和Masson染色观察肺组织病理学形态,ELISA法检测血清转化生长因子β_(1)(TGF-β_(1))和血小板衍生生长因子(PDGF)水平,Western blot法检测肺组织中β-catenin、CyclinD1和Axin蛋白表达情况,RT-PCR法检测肺组织中wnt3a、wnt5a、β-catenin、Axin、CyclinD1 mRNA表达情况。结果与正常组比较,模型组大鼠肺泡壁断裂,肺泡间隔增厚,炎性细胞浸润明显,气道壁、气道平滑肌厚度及气道上皮下胶原纤维沉积增加显著;血清PDGF、TGF-β_(1)水平均明显升高(P均<0.05);肺组织中β-catenin、CyclinD1蛋白及wnt3a、wnt5a、β-catenin、CyclinD1 mRNA相对表达量均明显升高(P均<0.05),Axin蛋白及mRNA相对表达量均明显降低(P均<0.05)。与模型组比较,阳和平喘颗粒各组和桂龙咳喘宁组气道重塑改善;阳和平喘颗粒中、高剂量组和桂龙咳喘宁组血清PDGF、TGF-β_(1)水平均明显降低(P均<0.05);阳和平喘颗粒高剂量组肺组织中β-catenin、CyclinD1蛋白及wnt3a、wnt5a、β-catenin、CyclinD1 mRNA相对表达量均明显降低(P均<0.05),Axin蛋白及mRNA相对表达量均明显升高(P均<0.05)。结论补肾活血化痰方可通过调节Wnt/β-catenin信号通路而改善COPD气道重塑。Objective It is to observe the effect of decoction for tonifying the kidney,activating blood circulation and resolving phlegmon on Wnt/β-catenin signaling pathway and airway remodeling in the rats with chronic obstructive pulmonary disease(COPD).Methods Forty-eight male SD rats were randomly divided into normal group,model group,Guilong Kechuanning group and low,medium and high dose groups of Yanghe Pingchuan granules,with 8 rats in each group.The rats in all groups except for the normal group were smoked plus intratracheal drops of lipopolysaccharide to establish COPD models.After successful modeling,the Guilong Kechuanning group was given Guilong Kechuanning 3.5 mL/100 g by gavage,the low,medium and high dose groups of Yanghe Pingchuan granules were respectively given Yanghe Pingchuan granules 1.75 g/(kg·d),3.5 g/(kg·d),7 g/(kg·d)by gavage,the normal group and model group were given normal saline by gavage,all continuously treated for 12 weeks.The pathological changes of lung tissue were observed by HE staining and Masson staining,the levels of serum transforming growth factorβ_(1)(TGF-β_(1))and platelet-derived growth factor(PDGF)were measured by ELISA,the expression ofβ-catenin,CyclinD1 and Axin protein in lung tissues were detected by Western blot,and the expression of wnt3a,wnt5a,β-catenin,Axin and CyclinD1 mRNA in lung tissues were detected by RT-PCR.Results Compared with the normal group,fractured alveolar wall,thickened alveolar septum,significant inflammatory cell infiltration,and significant increases of thickness of airway wall and airway smooth muscle and airway subepithelial collagen fiber deposition were found in the rats of the model group;the levels of serum PDGF and TGF-β_(1) were significantly increased(all P<0.05),the relative expression ofβ-catenin,CyclinD1 protein and wnt3a,wnt5a,β-catenin,CyclinD1 mRNA in lung tissues were significantly increased(all P<0.05),and the relative expression of Axin protein and mRNA were significantly decreased(P<0.05)in the rats of the model group.Com

关 键 词：慢性阻塞性肺疾病 补肾活血化痰方 WNT/Β-CATENIN信号通路 气道重塑 

分 类 号：R-332[医药卫生]