扶正解毒化瘀方通过NLRP3炎性体减轻多重耐药铜绿假单胞菌慢性肺炎肺损伤的作用机制

Mechanism of Fuzheng Jiedu Huayu Formula on lung injury of chronic pneumonia induced by multidrug resistant pseudomonas aeruginosa through NLRP3 inflammatory body

目的:观察扶正解毒化瘀方通过干预NLRP3炎性体减轻多重耐药铜绿假单胞菌(MDRPA)慢性肺炎肺损伤的作用机制。方法:将大鼠随机分为正常组、模型组、中药组、西药组、中+西组,通过经口气管插管法建立MDRPA慢性肺炎大鼠模型。中药组予扶正解毒化瘀方灌胃,每次1.4 g/mL,2次/d;西药组予哌拉西林他唑巴坦钠腹腔注射,每8小时1次;中+西组为两药联用。观察各时点肺组织病理变化。通过qPCR和Western blot观察NLRP3炎性体相关指标的基因和蛋白表达。结果:与模型组比较,中药组NLRP3 mRNA和Caspase-1 mRNA水平在第14天和21天显著降低(P<0.05),中药组、西药组和中+西组第14天时NLRP3、IL-1β蛋白表达水平均显著下降(P<0.05)。与模型组比较,中药组在第7、14天肺泡结构更完整,免疫细胞浸润更少,第21天时免疫细胞浸润和纤维细胞形成也更少。结论:扶正解毒化瘀方能明显减轻MDRPA慢性肺炎大鼠肺组织损伤,可能是通过调节NLRP3炎性体的表达而发挥作用。

Objective: To investigate the mechanism of Fuzheng Jiedu Huayu Formula in alleviating lung injury in rats with multidrug resistant pseudomonas aeruginosa(MDRPA) chronic pneumonia by intervening NLRP3 inflammatory body.The rats were divided into the normal group,model group,Chinese medicine group,western medicine group,Chinese+western group randomly. The rat model of MDRPA chronic pneumonia was established by oral tracheal intubation. The Chinese medicine group was given Fuzheng Jiedu Huayu Formula by gavage,1.4 g/mL per time,2 times/d. The western medicine group was given piperacillin tazobactam sodium by intraperitoneal injection,q8 h. The Chinese+western group was given the two medicine.The pathological changes of lung tissues were observed at various time points. The expression of genes and proteins related to NLRP3 inflammatory body was observed by qPCR and Western blot. Results: Compared with the model group,the levels of NLRP3 mRNA and Caspase-1 mRNA in the Chinese medicine group decreased significantly on the 14th and 21st days(P<0.05),NLRP3 and IL-1β protein expression decreased significantly in the traditional Chinese medicine group,western medicine group and Chinese+western medicine group on the 14th day(P<0.05). Compared with the model group,the Chinese medicine group had more complete alveolar structure,less immune cell infiltration on the 7th and 14th days,and less immune cell infiltration and fibroblast formation on the 21st day. Conclusion: Fuzheng Jiedu Huayu Formula can significantly reduce the lung injury in rats with chronic pneumonia caused by MDRPA,which may play a role by regulating the expression of NLRP3 inflammatory body.