摘要
目的:分析高迁移率族蛋白1(High mobility group protein 1,HMGB1)对大鼠糖尿病足溃疡炎症的影响及机制。方法:经腹腔注射链脲佐菌素建立糖尿病大鼠模型,并在大鼠的双后足背部做一3 mm×7 mm的全层矩形皮肤缺损,接种质控菌株。将建模成功的大鼠随机分成:模型组(等量生理盐水)、低剂量组(12.5μg·kg^-1·d^-1)、中剂量组(25μg·kg^-1·d^-1)和高剂量组(50μg·kg^-1·d^-1),每组6只,每天单次腹腔注射,连续给药14 d。另取6只大鼠作为空白组(等量生理盐水)。于规定时间对各组大鼠创面愈合率、微血管密度(Microvascular density,MVD)、组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)、CD45、Toll样受体4(Toll like receptor 4,TLR4)、核因子κB(Nuclear factor kappa-B,NF-κB)、白介素-1β(Interleukin-1β,IL-1β)、白介素-6(Interleukin-6,IL-6)、IL-8(Interleukin-8,IL-8)和肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)m RNA或蛋白表达量进行检测。结果:与对照组相比,模型组大鼠创面治愈率和微血管密度均较低,VEGF、CD45、TLR4、NF-κB、IL-1β、IL-6、IL-8和TNF-αm RNA或蛋白表达量均较高(P<0.05)。与模型组相比,三个剂量组大鼠创面治愈率和微血管密度均明显降低(P<0.05),VEGF、CD45、TLR4、NF-κB、IL-1β、IL-6、IL-8和TNF-αm RNA或蛋白表达量均较高(P<0.05)。且随着HMGB1注射剂量增大,创面愈合率、血管生成明显减少(P<0.05),炎症因子表达量显著升高(P<0.05)。结论:HMGB1对大鼠糖尿病足溃疡炎症有促进作用,机制可能与HMGB1/TLR4/NF-κB信号通路相关。
Objective:To analyze the effect and mechanism of High mobility group protein 1(HMGB1)on the inflammation of diabetic foot ulcer in rats.Methods:The diabetic rat model was established by intraperitoneal injection of streptozotocin,and a full-thickness rectangular skin defect of 3 mm×7 mm was made on the back of two hind feet of the rat,and inoculation of quality control strains as successful model of foot ulcer.The rats were randomly divided into three groups:the model group(equal amount of normal saline),the low dose group(12.5μg·kg^-1·d^-1),the medium dose group(25μg·kg^-1·d^-1)and the high dose group(50μg·kg^-1·d^-1).Each group consisted of six rats,which were injected intraperitoneally once a day for 14 days.Another 6 rats were taken as the blank group.The wound healing rate,microvascular density(MVD),vascular endothelial growth factor(VEGF),CD45,toll like receptor 4(TLR4),nuclear factor kappa B(NF-κB),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)m RNA or protein expression were detected.Results:Compared with the control group,the wound healing rate and microvessel density of the model group were lower,the expression of VEGF,CD45,TLR4,NF-κB,IL-1β,IL-6,IL-8 and TNF-αm RNA or protein were higher(P<0.05).Compared with the model group,the wound healing rate and MVD of the three dose groups were lower,the expression of VEGF,CD45,TLR4,NF-κB,IL-1β,IL-6,IL-8 and TNF-αm RNA or protein were higher(P<0.05).Compared with the model group,the wound healing rate and MVD of the three dose groups were significantly reduced(P<0.05),the expression levels of VEGF,CD45,TLR4,NF-κB,IL-1β,IL-6,IL-8 and TNF-αm RNA or protein were higher(P<0.05).With the increase of HMGB1 injection dose,the wound healing rate and angiogenesis decreased significantly(P<0.05),and the expression of inflammatory factors increased significantly(P<0.05).Conclusion:HMGB1 could promote the inflammation of diabetic foot ulcer in rats,and the mechanism may be related to HMGB1/TLR4/NF-κB s
作者
谢瑞敏
李想
李强强
魏建仝
王勇平
XIE Rui-min;LI Xiang;LI Qiang-qiang;WEI Jian-tong;WANG Yong-ping(Department of Orthopedics,First Hospital of Lanzhou University,Lanzhou,Gansu,730000,China;The First Clinical Medical College of Lanzhou University,Lanzhou,Gansu,730000,China;Department of Orthopedics,Zhangye People's Hospital,Hexi University,Zhangye,Gansu,734000,China)
出处
《现代生物医学进展》
CAS
2020年第13期2430-2434,2429,共6页
Progress in Modern Biomedicine
基金
甘肃省卫生行业科研计划项目(GSWSKY-2015-53)
甘肃省科技厅创新基地和人才计划项目(18JR3RG211)
兰州大学第一临床医学院卓越计划想项目(20180060130)。
