海南医科大学学报2025，Vol.31Issue(23)：1802-1811,10.DOI:10.13210/j.cnki.jhmu.20241219.002
基于NEK7/NLRP3/ASC信号通路探讨平喘宁方抑制细胞焦亡调控哮喘大鼠气道炎症的机制
Mechanism of Pingchuanning Formula inhibiting pyroptosis to regulate airway inflammation in asthmatic rats based on the NEK7/NLRP3/ASC signaling pathway
摘要
Abstract
Objective:To explore the effects and mechanism of action of the classical formula of Pingchuanning(PCN)and MCC950 inhibitor on airway inflammation in asthmatic rats from the perspective of pyroptosis.Methods:A total of 70 SD rats were randomly divided into 7 groups:the normal group,the model group,the PCN group,the MCC950 group,the PCN+MCC950 inhibitor group,the dexamethasone group,and the Guilong Kechuanning group.A concentration of 10%ovalbumin(OVA)was injected subcutaneously via the abdominal cavity and the limbs to induce allergy,and the rat model of asthma was stimulated by the combination of 2%OVA nebulisation and cold air(2‒4℃).The intervention was continued for 3 weeks with ga-vage and aerosolization of PCN(7.289 g/kg),MCC950(10 mg/kg),PCN(7.289 g/kg)+MCC950(10 mg/kg),dexametha-sone(0.405 mg/kg),and Guilong Kechuanning(0.405 g/kg).After the final stimulation,airway inflammation was observed by H&E and PAS staining in lung tissue of the rats.The levels of IL-1β,IL-18,and IL-6 in serum and BALF were detected by ELI-SA,the mRNA expression levels of NEK7,NLRP3,ASC,and Caspase-1 were detected by RT-PCR,and the protein expres-sion levels of NEK7,NLRP3,ASC,and Caspase-1 were detected by Western blot.Results:Compared to the normal group,rats in the model group had reduced diet,weight loss,emotional irritability,shortness of breath,airway inflammatory cell infiltra-tion,goblet cell proliferation,and there was a significant increase in IL-1β,IL-18,and IL-6 inflammatory factors in the serum and BALF;mRNA and protein expression levels of NEK7,NLRP3,ASC,and Caspase-1 were elevated.Compared to the model group,rats in the PCN,MCC950,and PCN+MCC950 groups showed a gradual improvement in diet,alleviation of asthma,sig-nificant reduction in airway inflammatory cell infiltration,and reduction of IL-1β,IL-18,and IL-6 inflammatory factors in serum and BALF(P<0.001),as well as suppression of NEK7,NLRP3,ASC,and Caspase-1 mRNA and protein expression(P<0.001).Conclusion:PCN and MCC950 inhibitor can significantly improve airway inflammation induced by OVA combined with cold stimulation in asthmatic rats and correlate with the NEK7/NLRP3/ASC signaling pathway and pyroptosis,in which the effi-cacy of PCN combined with MCC950 is more pronounced,suggesting that the combined treatment is more effective than a single compound or Western medicine.关键词
平喘宁/MCC950抑制剂/哮喘/NEK7/NLRP3/细胞焦亡Key words
Pingchuanning/MCC950 inhibitor/Asthma/NEK7/NLRP3/Pyroptosis分类
医药卫生引用本文复制引用
LIU Jiaxin,FANG Wenkai,YUAN Yamei,YE Weidong,LI Qiuhui,FANG Xiangming..基于NEK7/NLRP3/ASC信号通路探讨平喘宁方抑制细胞焦亡调控哮喘大鼠气道炎症的机制[J].海南医科大学学报,2025,31(23):1802-1811,10.基金项目
This study was supported by the Natural Major Programs of Universities in Anhui Province(2024AH040157) （2024AH040157）
Academic Funding Program for Top Talents in Disciplines(Specialties)in Anhui Colleges and Universities(gxbjZD2021054) 安徽省高校自然重大项目(2024AH040157) （Specialties）
安徽省高校学科(专业)拔尖人才学术资助项目(gxbjZD2021054) （专业）
