赤芍对慢性阻塞性肺疾病大鼠气道重塑的影响及机制研究

Effects and mechanism of Radix Paeoniae Rubra on airway remodeling of cigarette smoke mediated-COPD model rats

目的:探讨赤芍对烟熏慢性阻塞性肺疾病(COPD)模型大鼠气道重塑的作用。方法:采用烟熏法建立大鼠COPD模型,将48只SPF级健康雄性SD大鼠按照随机数字表法分为正常组,模型组,布地奈德组(BUD),赤芍低、中、高剂量组,每组8只,分别给予36周对应处理,观察HE和Masson染色肺部病理变化、MIQAS分析测定小支气管平滑肌和肺小动脉平滑肌厚度、BUXCO测定肺功能、ELISA检测血清IL-8和IL-10以及肺泡灌洗液TGF-β1、MMP-2、MPP-9以及TIMP-1水平。结果:与正常组比较,模型组肺功能下降,肺组织病理变化较重,气道和肺小动脉平滑肌增厚,细胞因子IL-8、TGF-β1、MMP-2、MMP-9及TIMP-1升高(P<0.01),IL-10降低(P<0.01);与模型组比较,赤芍降低促炎因子IL-8(P<0.01),升高抑炎因子IL-10(中剂量组P<0.05),抑制TGF-β1、MMP-2、MMP-9、TIMP-1表达(P<0.01),改善气道炎性反应和重塑;与BUD相比较,赤芍组部分参数有显著差异性。结论:赤芍能够改善COPD大鼠气流阻塞和气道重塑,延缓肺功能下降。

Objective:To investigate the effects of Radix Paeonia Rubra on airway remodeling in chronic obstructive pulmonary disease(COPD) rats with the method of establishing the cigarette-smoking rat model of COPD.Methods:Totally 48 SPF healthy male Sprague Dawley(SD) rats were randomly divided into 6 groups:normal group,model group,Budesonide(BUD) group,and the low,middle and high dose groups,with 8 rats for each group respectively for 36 weeks treatment.After 36 weeks,the pulmonary function was evaluated by BUXCO system and the morphology changes of the lungs were observed with HE and Masson staining.The serum IL-8 and IL-10 and TGF-β1,MMP-2,MMP-9,TIMP-1 level in BALF were detected by ELISA-kit assay.Results:Compared with the normal group,the lung function of the model group was decreased,the pathological changes of lung tissue were heavier,and the thickness of airway and pulmonary arterioles was thickened.Meanwhile the level of IL-8 and TGF-β1,MMP-2,MMP-9 and TIMP-1 were partially significantly increased(P<0.01) while the level of IL-10 was partially decreased(P<0.01).Compared with the model group,Radix Paeonia Rubra could decrease the level of IL-8,inhibit the expression of TGF-β1,MMP-2,MMP-9 and TIMP-1 significantly(P<0.01),and increase the level of IL-10 significantly(middle dosage,P<0.05).In some parameters,there were significant differences between BUD and SB groups.Conclusion:Radix Paeonia Rubra could significantly improve the airflow obstruction,airway remodeling and delay the decline of lung function in COPD rats.