摘要
目的探讨N-乙酰半胱氨酸(NAC)对脓毒症肺损伤的作用及机制。方法 48只Balb/c小鼠随机分为对照组、模型组、NAC低剂量组、中剂量组、高剂量组和阳性药组(n=8)。给予LPS前1 h,腹腔注射药物干预研究。给予LPS 6 h后麻醉,收集肺泡灌洗液(BALF)和血清。苏木精-伊红染色检测肺损伤病理变化;ELISA检测BALF和血清中TNF-α、IL-6和IL-1β含量;Western blot检测组织中NLRP3、Caspase1和ASC蛋白水平;流式细胞术分析M2型巨噬细胞表型;商用试剂盒测量组织中MDA、MPO、SOD、GSH和ROS含量。结果与模型组比较,NAC组小鼠肺损伤显著缓解,且BALF和血清中TNF-α、IL-6和IL-1β含量减少。NAC组较模型组小鼠BALF中M2型巨噬细胞表型增强,且NLRP3、Caspase1和ASC蛋白下调。NAC组小鼠肺组织中MDA、MPO和ROS含量减少,同时,SOD和GSH含量增加。结论 N-乙酰半胱氨酸对急性肺损伤具有保护作用,且可能与抑制ROS-NLRP3信号通路诱导巨噬细胞的M2型分化有关。
To investigate the roles and mechanism of N-acetylcysteine on septic lung injury, total of 48 Balb/c mice were included and randomly divided into control group, model group, NAC low-dose group, medium-dose group, high-dose group and positive drug group, with 8 mice in each group. Corresponding drugs were injected intra-peritoneally one hour before the administration with LPS. Six hours after LPS administration, mice were anesthe-tized, and then the BALF and serum were collected. The pathological changes of lung injury were detected by hema-toxylin-eosin staining;the TNF-α, IL-6 and IL-1β levels in BALF and serum were analyzed by ELISA;the NL-RP3, Caspase1 and ASC protein levels in tissues were detected by Western blotting;the M2 type macrophage pheno-type was analyzed by flow cytometry, while the contents of MDA, MPO, SOD, GSH and ROS in tissues were analyzed by commercial kits. Compared with the model group, the lung injury in the NAC group was significantly relieved,and the contents of TNF-α, IL-6 and IL-1β in BALF and serum were reduced. Compared with the model group, the phenotype of M2 macrophages in the BALF was enhanced, while NLRP3, Caspase1 and ASC proteins were downregulated in NAC group. The contents of MDA, MPO and ROS in the lung tissue were decreased, and the contents of SOD and GSH were increased in the NAC group. In conclusion, N-acetylcysteine has protective effects on acute lung injury, and the mechanism may related to the inhibition of ROS-NLRP3 signaling pathway and induction of M2macrophage differentiation.
作者
张伟
何正琼
吴希
ZHANG Wei;HE Zhengqiong;WU Xi(Department of Critical Medicine,Nuclear Industrial 416 Hospital&Second Affiliated Hospital of Chengdu Medical College,Chengdu 610051,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2021年第6期489-496,共8页
Immunological Journal