基于TLR4/NF-κB通路研究丹皮酚延缓气道重塑治疗哮喘的作用机制

Study on the mechanism of paeonol delaying airway remodelingin asthma based on TLR4/NF-κB pathway

目的基于Toll样受体4/核转录因子-κB(TLR4/NF-κB)信号通路,研究丹皮酚对哮喘大鼠气道重塑的影响,探讨其治疗哮喘的可能机制。方法随机将SD大鼠分为正常对照组、哮喘模型组、地塞米松组和丹皮酚低剂量组(75 mg·kg^(-1))、中剂量组(150 mg·kg^(-1))、高剂量组(300 mg·kg^(-1))。采用卵白蛋白(OVA)致敏法制备哮喘大鼠模型,治疗组采用雾化吸入给药。采用HE染色检测肺组织病理形态改变;采用计算机图像分析肺组织气道壁厚度;采用免疫组织化学法检测大鼠肺组织中NF-κB蛋白的表达;采用RT-PCR法检测大鼠肺组织中TLR4 mRNA的表达。结果与正常对照组比较,哮喘模型组大鼠出现严重的病理损伤和气道重塑,气道内壁厚度(WAi/Pbm)、气道壁厚度(WAt/Pbm)、气管平滑肌厚度(WAm/Pbm)和肺组织中TLR4及NF-κB表达升高(P<0.05)。经地塞米松和丹皮酚雾化吸入治疗后,各组大鼠WAi/Pbm、WAt/Pbm和WAm/Pbm、肺组织中TLR4及NF-κB表达降低(P<0.05),且呈现剂量依赖性。结论丹皮酚可有效改善哮喘大鼠气道重塑,其机制可能与抑制哮喘大鼠肺组织中TLR4/NF-κB信号通路有关。

Objective To investigate the mechanism of paeonol delaying airway remodeling in asthma based on TLR4/NF-κB signaling pathway,to explore the possible mechanism of paeonol in treating asthma.Methods Sprague-dawley rats were randomly divided into normal control group,asthma model group,dexamethasone group,low-dose paeonol group(75 mg·kg^(-1)),middle-dosepaeonol group(150 mg·kg^(-1))and high-dose paeonol group(300 mg·kg^(-1)).The asthma rat model was established by ovalbumin(OVA)sensitization.The treatment group was treated by aerosol inhalation.The pathological changes of lung tissue were detected by HE staining;The thickness of airway wall was analyzed by computer image analysis;The expression of NF-κB protein was detected by immunohistochemistry,the expression of TLR4 mRNA was detected by RT-PCR.Results Compared with the normal control group,the asthmatic model group showed severe pathological injury and airway remodeling,WAi/Pbm,WAt/Pbm,WAm/Pbm and the expression of TLR4 and NF-κB in lung tissue were increased(P<0.05).After treated with artesunate and paeonol,WAi/Pbm,WAt/Pbm and WAm/Pbm,the expression of TLR4 and NF-κB in lung tissue were decreased(P<0.05).Conclusion Paeonol can effectively improve airway remodeling in asthmatic rats,and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway in the lung tissue of asthmatic rats.