摘要
目的 研究血必净注射液调控高迁移率族蛋白1(HMGB1)/Toll样受体4(TLR4)/核因子-κB(NF-κB)通路对脓毒症小鼠肺损伤的保护作用。方法 雄性C57BL/6小鼠随机分为对照组,模型组和低、中、高剂量血必净组,阴性对照(NC)组,NC+模型组,NC+高剂量血必净组,HMGB1+高剂量血必净组。采用盲肠结扎穿孔术建立脓毒症肺损伤模型,造模前给予NC慢病毒或HMGB1慢病毒尾静脉注射,造模当天给予血必净注射液(剂量5、10、15mL/kg)腹腔注射,2次/d,连续3 d,末次给药后24 h进行取材和检测。比较各组间肺组织病理改变,湿重(W)/干重(D)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,裂解型Caspase-3、HMGB1、TLR4、NF-κB表达水平的差异。结果 模型组小鼠肺组织出现肺损伤的病理改变,W/D、TNF-α、IL-1β、IL-6、MDA的含量及裂解型Caspase-3、HMGB1、TLR4、NF-κB的表达水平均高于对照组,SOD的含量低于对照组(P<0.05)。不同剂量血必净组小鼠肺损伤的病理改变减轻,W/D、TNF-α、IL-1β、IL-6、MDA的含量及裂解型Caspase-3、HMGB1、TLR4、NF-κB的表达水平低于模型组,SOD的含量高于模型组(P<0.05)。HMGB1+高剂量血必净组小鼠肺损伤的病理改变加重,W/D、TNF-α、IL-1β、IL-6、MDA的含量及裂解型Caspase-3、HMGB1、TLR4、NF-κB的表达水平均高于NC+高剂量血必净组,SOD的含量低于NC+高剂量血必净组(P<0.05)。结论 血必净注射液对脓毒症小鼠肺损伤具有保护作用,并减轻炎症反应、氧化应激、细胞凋亡,其相关的分子机制为抑制HMGB1/TLR4/NF-κB通路。
Objective To investigate the protective effect of Xuebijing injection on lung injury in septic mice by regulating the high mobility group protein box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.Methods Male C57BL/6 mice were randomly divided into control,model,low,medium and high dose of Xuebijing groups,negative control(NC)group,NC+model group,NC+high-dose of Xuebijing group,and HMGB1+high-dose of Xuebijing group.A sepsis-induced lung injury model was established using cecal perforation.Before modeling,the mice were intravenously injected with NC lentivirus or HMGB1 lentivirus via the tail vein.On the day of modeling,the mice were intraperitoneally injected with Xuebijing injection(5,10 and 15 mL/kg)twice a day for three consecutive days.Samples were collected and detected 24 h after the last administration.The pathological changes of lung tissue,wet weight(W)/dry weight(D),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA)and superoxide dismutase(SOD)contents,the expression levels of Cleaved caspase-3,HMGB1,TLR4 and NF-κB were compared among all groups.Results Pathological changes of lung injury were observed in the model group,with increases in the levels of W/D,TNF-α,IL-1β,IL-6,MDA,and expression of Cleaved caspase-3, HMGB1, TLR4, NF-κB, and decreased SOD content compared with the control group (P<0. 05).In Xuebijing treatment groups, pathological changes in lung injury were alleviated, with lower levels of W/ D, TNF-α,IL-1β, IL-6, MDA and expression of Cleaved caspase-3, HMGB1, TLR4, NF-κB, and higher SOD content than themodel group (P<0. 05). The HMGB1+high-dose of Xuebijing group showed aggravated lung injury pathology, withhigher levels of W/ D, TNF-α, IL-1β, IL-6 and MDA, and expression of Cleaved caspase-3, HMGB1, TLR4 and NF-κB, and lower SOD content than the NC+high-dose of Xuebijing group (P<0. 05). Conclusions Xuebijing injectionhas protective effect on lung injury in septic mice and alleviates inflammation, oxidative
作者
张志斌
李瑞彤
郑卫伟
林雪容
牛宁宁
王慧
苑萌
韩树池
薛乾隆
ZHANG Zhibin;LI Ruitong;ZHENG Weiwei;LIN Xuerong;NIU Ningning;WANG Hui;YUAN Meng;HAN Shuchi;XUE Qianlong(Department of Emergency,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China)
出处
《徐州医科大学学报》
CAS
2024年第4期254-260,共7页
Journal of Xuzhou Medical University
基金
河北省卫生健康委科研基金项目(20231452)。
