基于TGF-β1/Smads通路探讨龟鹿补肾丸对COPD大鼠气道重塑的影响  

Effect of Guilu Bushen Wan on airway remodeling in COPD rats based on TGF-β1/Smads pathway

作　　者：陈聪 陈志钊 李志强 陈曌 江涛 耿春贤 CHEN Cong;CHEN Zhizhao;LI Zhiqiang;CHEN Zhao;JIANG Tao;GENG Chunxian(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangzhou Baiyunshan Huacheng Pharmaceutical Co.,Ltd.,Guangzhou 510555,China;Laboratory Animal Center,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广州白云山花城药业有限公司,广东广州510555 [3]广东药科大学实验动物中心,广东广州510006

出　　处：《广东药科大学学报》2024年第3期25-32,共8页Journal of Guangdong Pharmaceutical University

基　　金：广州黄埔区生物医药产业专项资金项目(KC20200608-064)。

摘　　要：目的探究龟鹿补肾丸对慢性阻塞性肺疾病(COPD)模型大鼠气道重塑的干预作用及其机制。方法将60只SPF级SD大鼠随机分为正常对照组,模型组,龟鹿补肾丸低、中、高剂量(1.8 g/kg、3.6 g/kg、7.2 g/kg)组和氨茶碱(30.0 mg/kg)组,每组10只。采用气管内滴注脂多糖联合烟熏法复制COPD模型,自第29天起给予正常对照组、模型组灌胃生理盐水,其余各治疗组分别给予相应药物,连续给药28 d。实验第57天检测肺功能、肺组织病理学变化;ELISA法检测支气管肺泡灌洗液(BALF)中MMP-9、MMP-12、TIMP-1含量;IHC法检测肺组织TGF-β1、COL-I、α-SMA的表达;Western blot法检测肺组织TGF-β1、p-Samd2、p-Samd3的表达。结果与正常对照组相比,模型组大鼠呼气峰流速(PEF)、吸气峰流速(PIF)、每分钟通气量(MV)、呼出50%潮气量时呼气流速(EF50)下降,肺组织炎性细胞浸润明显,平均肺泡数(MAN)减少、肺平均内衬间隔值(MLI)增加,气道胶原纤维沉积明显增多,肺泡灌洗液(BALF)中MMP-12、TIMP-1含量升高,肺组织TGF-β1、p-Samd2、p-Samd3、COL-I、α-SMA表达上调。经龟鹿补肾丸干预后,可升高PIF、PEF、MV、EF50,减轻肺组织炎性细胞浸润,MAN值增加,MLI值减少,抑制胶原沉积,降低MMP-12、TIMP-1含量,下调肺组织TGF-β1、p-Samd2、p-Samd3、COL-I、α-SMA的表达。结论龟鹿补肾丸可以改善COPD模型大鼠的肺功能,减轻气道重塑程度,其机制可能与调节TGF-β1/Smads信号通路有关。Objective To explore the intervention effect and mechanism of Guilu Bushen Wan on airway remodeling in rats with chronic obstructive pulmonary disease(COPD).Methods Sixty SPF SD rats were randomly divided into normal control group,model group,and low,medium,and high doses of Guilu Bushen Wan groups(1.8 g/kg,3.6 g/kg,7.2 g/kg),and aminophylline group(30.0 mg/kg).The COPD model was replicated by intratracheal infusion of lipopolysaccharide combined with smoking.Starting from the 29th day,the normal control group and model group were given physiological saline by gavage,while the other treatment groups were given corresponding drugs for 28 consecutive days.On the 57th day of the experiment,lung function and pathological changes in lung tissue were detected.ELISA was used to detect the levels of MMP-9,MMP-12,and TIMP-1 in bronchoalveolar lavage fluid(BALF).IHC method was used to detect the expression of TGF-β1,COL-I andα-SMA in lung tissue.Western blot was used to detect the expression of TGFβ1,p-Samd2 and p-Samd3 in lung tissue.Results Compared with the control group,PEF,PIF,MV and EF50 of lung function were decreased in the model group.The infiltration of inflammatory cells in lung tissue was obvious,MAN value was decreased,and MLI value and the deposition of airway collagen fiber were significantly increased.The contents of MMP-12 and TIMP-1 in BALF were increased,and the expressions of TGF-β1,p-Samd2,p-Samd3,COL-I andα-SMA in lung tissue were upregulated.After treatment with Guilu Bushen Wan,PIF,PEF,MV and EF50 were increased.The infiltration of inflammatory cells in lung tissue was reduced,MAN value was increased,and MLI value and the deposition of airway collagen fiber were lowered.The contents of MMP-12 and TIMP-1 in BALF and the expression of TGF-β1,p-Samd2,p-Samd3,COL-I andα-SMA in lung tissue were decreased.Conclusion Guilu Bushen Wan can improve lung function and reduce airway remodeling in COPD rats,which may be related to regulating TGF-β1/Smads signaling pathway.

关 键 词：龟鹿补肾丸 慢性阻塞性肺疾病 肺功能 气道重塑 TGF-β1/Smads通路 

分 类 号：R285.5[医药卫生—中药学]