鱼腥草提取物对慢性阻塞性肺疾病急性加重期大鼠肺功能的影响及对TLR4/NF-κB信号通路的调控作用

Effects of Houttuynia Cordata Extract on Lung Function of COPD Acute Exacerbation Rats and Regulation of TLR4/NF-κB Signal Pathway

目的:探讨鱼腥草提取物对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)急性加重期大鼠肺功能的影响及对Toll样受体4(toll-like receptor 4,TLR4)/核转录因子κB(nuclear factor-κB,NF-κB)信号通路的调控作用。方法:50只大鼠分为对照组、COPD组、鱼腥草低剂量(1.25 g·kg^(-1))组、鱼腥草中剂量(2.50 g·kg^(-1))组、鱼腥草高剂量(5.00 g·kg^(-1))组,各10只,复制COPD急性加重期模型(对照组除外)后,连续4周给予相应的药物。比较各组大鼠肺功能指标;检测肺泡灌洗液(alveolar lavage fluid,BALF)中炎症因子水平;观察肺组织病理变化;比较肺组织中TLR4 mRNA、NF-κB mRNA及蛋白表达。结果:与COPD组比较,鱼腥草低、中、高剂量组用力呼气峰流速(peak expiratory flow rate,PEF)、第0.3秒用力呼气容积(forced expiratory volume at 0.3 second,FEV0.3)/FVC、最大呼气中期流速(maximum middle expiratory flow rate,MMEF)均升高;BALF中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)水平均明显降低(P<0.05),且具有剂量依赖性;病理结果显示,COPD组肺组织存在典型病理改变,且大量炎性细胞浸润,鱼腥草各剂量组肺组织上述病理改变较COPD组均有所减轻,且鱼腥草高剂量组改善最明显,但仍有少量炎症细胞浸润;同时鱼腥草(低、中、高剂量)组肺组织中TLR4 mRNA、NF-κB mRNA和蛋白相对表达量均明显降低(P<0.05)。结论:鱼腥草提取物可有效改善COPD急性加重期大鼠肺功能,减轻肺病理损伤,推测与抑制TLR4/NF-κB信号通路有关。

Objective:To investigate the effects of houttuynia cordata extract on lung function and the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signal pathway in rats with chronic obstructive pulmonary disease(COPD)acute exacerbation.Methods:50 rats were divided into control group,COPD group,low(1.25 g·kg^(-1)),medium(2.50 g·kg^(-1)),and high(5.00 g·kg^(-1))dose houttuynia cordata groups,each with 10 rats.After establishing the rat model of acute exacerbation of COPD(except the control group),each group was given corresponding drugs for 4 consecutive weeks.The lung function indexes and the levels of inflammatory factors in the alveolar lavage fluid(BALF)of each group were compared,the pathological changes of lung tissues were observed,and the expressions of TLR4 mRNA and NF-κB mRNA and protein in lung tissues were compared.Results:Compared with COPD group,forced vital capacity(FVC),peak expiratory flow rate(PEF),forced expiratory volume(FEV0.3)/FVC and maximum middle expiratory flow rate(MMEF)of houttuynia cordata groups were increased,TNF-α,IL-6,and IL-1βin BALF decreased,all of which were dose-dependent(P<0.05).The pathological results showed that the lung tissues of the COPD group had typical pathological changes,with a large number of inflammatory cells infiltrated.The above-mentioned pathological changes in each group of Houttuynia cordata were alleviated compared with the COPD group,and the improvement in the high dose houttuynia cordata group was the most significant,but a small amount of infiltration of inflammatory cells still exist.Compared with the COPD group,the relative expressions of TLR4 mRNA,NF-κB mRNA,and protein in lung tissue of low,medium,and high dose houttuynia cordata group decreased,all of which were dose-dependent(P<0.05).Conclusion:Houttuynia cordata extract can effectively improve lung function and reduce lung pathological damage in rats with acute exacerbation of COPD,which is speculated related to the inhibition of TLR4/NF-κB signal pathway.