摘要
目的探讨青藤碱对小鼠急性肺损伤保护作用及机制。方法将48只小鼠通过随机数字表法分为假手术组、模型组、青藤碱低剂量组和青藤碱高剂量组,每组12只。通过气道滴注脂多糖(LPS)(0.5mg/kg)建立急性肺损伤小鼠模型,给予不同剂量(40、160mg/kg)青藤碱治疗,ELISA检测血清炎症因子肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)、单核细胞趋化因子1(MCP-1)含量;Western blot检测胞外信号调控激酶1/2(ERK1/2)/核因子κB(NF-κB)信号通路的激活情况;苏木素-伊红(HE)染色检测肺脏病理变化;CD68免疫荧光检测巨噬细胞浸润情况。结果 (1)ELISA检测血清炎症因子含量:与模型组比较,低、高剂量青藤碱均可明显减少血清炎症因子含量[TNF-α:(28.20±8.32)pg/m L、(20.17±5.87)pg/m L比(38.00±9.20)pg/m L,P<0.05;IL-6:(37.23±9.43)pg/m L、(25.64±4.34)pg/m L比(56.23±11.94)pg/m L,P<0.05;IL-1β:(56.98±5.17)pg/m L、(43.09±4.45)pg/m L比(73.21±13.23)pg/m L,P<0.05;MCP-1:(32.12±7.83)pg/m L、(24.35±7.46)pg/m L比(49.34±8.97)pg/m L,P<0.05],且呈剂量依赖性(P<0.05);(2)不同剂量青藤碱可以明显减轻肺脏巨噬细胞浸润及病理变化;(3)与模型组比较,青藤碱可以有效抑制ERK/NF-κB信号通路激活[pERK/ERK:(0.17±0.03)、(0.14±0.02)比(0.21±0.05),P<0.05;IκB/GAPDH:(0.18±0.03)、(0.31±0.07)比(0.08±0.02),P<0.05],并具有剂量依赖性(P<0.05)。结论青藤碱可能通过抑制ERK/NF-κB通路缓解LPS诱导小鼠急性肺损伤。
Objective To investigate the protective effect and mechanism of sinomenine on acute lung injury in mice.Methods Forty-eight mice were randomly divided into sham group,model group,low-and high-dose sinomenine groups,with 12 animals in each group.The mouse model of acute lung injury was established by airway infusion of lipopolysaccharide(0.5mg/kg).Sinomenine was given at different doses(40 and 160mg/kg,respectively).Serum levels of inflammatory cytokines TNF-α,Il-6,IL-1βand monocyte chemokine 1(MCP-1)were detected by ELISA.Western blot was used to test the activation of extracellular signaling kinase 1/2(ERK1/2)/nuclear factorκB(NF-κB)signaling pathway.Hematoxylin-Eosin(HE)staining was used to check pulmonary pathological changes.CD68 immunofluorescence was used to examine the infiltration of macrophages.Results(1)Serum levels of inflammatory cytokines by ELISA:compared to the model group,different doses of sinomenine significantly reduced serum levels of inflammatory cytokines,i.e.,TNF-α:[(28.20±8.32)and(20.17±5.87)vs(38.00±9.20)pg/mL,P<0.05],IL-6:[(37.23±9.43)and(25.64±4.34)vs(56.23±11.94)pg/mL,P<0.05],IL-1β:[(56.98±5.17)and(43.09±4.45)vs(73.21±13.23)pg/mL,P<0.05],MCP-1:[(32.12±7.83)and(24.35±7.46)vs(49.34±8.97)pg/mL,P<0.05],and in a dose-dependent manner(P<0.05).(2)Different doses of sinomenine significantly alleviated the infiltration and pathological changes of pulmonary macrophages.(3)Compared to the model group,sinomenine effectively inhibited the activation of ERK/NF-κB signaling pathway,i.e.,p-ERK/ERK:[(0.17±0.03)and(0.14±0.02)vs(0.21±0.05),P<0.05],IκB/GAPDH:[(0.18±0.03)and(0.31±0.07)vs(0.08±0.02),P<0.05],and in a dose-dependent manner(P<0.05).Conclusion Sinomenine could alleviate LPS-induced acute lung injury in mice by inhibiting ERK/NF-κB pathway.
作者
管静静
GUAN Jingjing(Department of Pharmacy,Lishui People's Hospital,Lishui,Zhejiang province,323000,China)
出处
《浙江中西医结合杂志》
2020年第9期709-712,I0002,共5页
Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
