槲皮素对支气管哮喘模型小鼠NLRP3/caspase-1炎症小体的抑制作用研究  

The Effect of Quercetin on Bronchial Asthma Mice through NLRP3/Caspase-1 Pathway

作　　者：许成辰 徐婷贞[1] 张敏 董春鸽 XU Chengchen;XU Tingzhen;ZHANG Min;DONG Chunge(Zhejiang Provincial Hospital of Traditional Chinese Medicine,Hangzhou 310000 Zhejiang,China)

机构地区：[1]浙江省中医院,浙江杭州310000

出　　处：《中药新药与临床药理》2019年第8期899-903,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：浙江省中医药科技计划项目(2016ZA067)

摘　　要：目的探究槲皮素对卵清蛋白(Optical Variable Attenuator,OVA)致小鼠支气管哮喘(Bronchial Asthma,BA)的治疗作用及机制。方法将BALB/c小鼠随机分为5组:对照组、OVA组、孟鲁司特组(0.004 g·kg-1)、槲皮素组(0.003、0.01 g·kg-1)。除对照组外,其余各组采用相同方式,给予OVA诱导哮喘模型。槲皮素治疗组在致敏后的第21~30天,连续给药10 d。观察动物的整体状态,评估小鼠哮喘程度;观察支气管病理学改变;取小鼠支气管肺泡灌洗液(BALF)、血清,采用ELISA法检测BALF和血清中肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)和白介素-6(IL-6)的水平;Western Blot法检测肺组织中NLRP3、ASC和Caspase-1的蛋白表达量变化。结果与对照组相比,OVA组出现明显的哮喘症状,BALF和血清中TNF-α、IL-1β和IL-6水平显著性升高(P <0.01,P <0.001),槲皮素(0.01 g·kg-1)组能够显著缓解小鼠的哮喘症状,抑制BALF及血清炎症因子水平的升高(P <0.05,P <0.01,P <0.001),且显著性降低肺组织中NLRP3、ASC和Caspase-1的蛋白表达(P <0.01,P <0.05,P <0.001)。结论槲皮素(0.01 g·kg-1)对OVA诱导的支气管哮喘模型小鼠具有明显的保护作用,与孟鲁司特的治疗效果相当,其机制可能与抑制NLRP3/ASC/Caspase-1炎症小体的信号通路有关。Objective To investigate the therapeutic effect and mechanism of quercetin on mouse bronchial asthma(BA)caused by ovalbumin(OVA).Methods BALB/c mice were randomly divided into 5 groups:control group,OVA group,montelukast 0.004 g·kg-1 group,quercetin 0.003,0.01 g·kg-1 groups.Except the control group,the other groups were given the OVA to induce asthma models.The quercetin administration groups were given continuously for 10 days during the 21 st to 30 th day after sensitization.The overall states of the animals were observed,the degrees of asthma in the mice were evaluated.The pathological changes of the bronchus were observed,the bronchoalveolar lavage fluid(BALF)and serum of the mice were collected for detection of the tumor necrosis factor(TNF)-α,interleukin(IL)-1βand IL-6 using ELISA.The levels of protein expression were detected by Western Blot.Results Compared with the control group,the OVA group showed obvious asthma symptoms,and the levels of TNF-α,IL-1βand IL-6 in BALF and serum were significantly increased,while two doses of quercetin(0.003,0.01 g·kg-1)significantly alleviated the asthma symptoms in mice,inhibited the increase of BALF and serum inflammatory factors(P<0.01),and significantly reduced the protein expression of NLRP3,ASC and Caspase-1 in lung tissue(P<0.01).Conclusion Quercetin has obvious protective effect on OVA-induced bronchial asthma in mice,which is equivalent to the therapeutic effect of montelukast.The mechanism may be related to the inhibition of NLRP3/ASC/Caspase-1 inflammatory signaling pathway.

关 键 词：支气管哮喘 槲皮素 NLRP3 ASC CASPASE-1 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]