高啸,沈莹.HMGB1-RAGE/TLRs-NF-κB信号通路中关键蛋白的表达与糖尿病肾病的关系[J].转化医学杂志,2020,9(6):331-334
HMGB1-RAGE/TLRs-NF-κB信号通路中关键蛋白的表达与糖尿病肾病的关系
Relationship between expression of key proteins in HMGB1-RAGE/TLRs-NF-κB signaling pathway and diabetic nephropathy
  
DOI:
中文关键词:  HMGB1-RAGE/TLRs-NF-κB信号通路  关键蛋白  糖尿病肾病
英文关键词:HMGB1-RAGE/TLRs-NF-κB signaling pathway  Key protein  Diabetic nephropathy
基金项目:
作者单位
高啸 华中科技大学同济医学院附属梨园医院内分泌科 
沈莹 华中科技大学同济医学院附属梨园医院老年病科 
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中文摘要:
      目的探究高迁移率族蛋白1(HMGB1)-晚期糖基化终产物受体(RAGE)/Toll样受体(TLRs)-核转录因子-κB(NF-κB)信号通路中关键蛋白的表达与糖尿病肾病的关系。方法C57BL/6雄性小鼠注射链脲菌素(STZ)建立糖尿病肾病(DN)模型列为DN组,生理盐水替代列为对照组,在DN组基础上给予胰岛素治疗列为治疗组,对比3组小鼠体质量、血糖、尿白蛋白定量和HMGB1-RAGE/TLRs-NF-κB信号通路中关键蛋白水平差异。另外给予DN组小鼠HMGB1拮抗剂A Box注射,观察注射前后小鼠尿白蛋白和肾组织切片变化。结果与对照组相比,DN组和治疗组小鼠体质量、血糖和尿白蛋白定量均明显增加(P<0.01);与DN组相比,治疗组上述各指标均明显下降(P<0.05)。建模完成后各时间段,DN组HMGB1、RAGE、TLR4,NF-κB蛋白水平均较对照组明显升高(P<0.05),治疗组小鼠HMGB1、RAGE、TLR2、TLR4和NF-κB蛋白水平均较对照组明显升高(P<0.05)。DN组和治疗组HMGB1、RAGE、TLR2、TLR4和NF-κB mRNA水平均明显高于对照组(P<0.01)。与DN组小鼠相比,治疗组小鼠各时间段上述几种蛋白和mRNA水平均明显偏低(P<0.05)。给予A Box后,生理盐水处理小鼠组织学染色无明显变化(P=0.933),DN模型小鼠肾小管间质胶原蛋白沉淀明显减少(P=0.013)。结论HMGB1-RAGE/TLRs-NF-κB信号通路关键蛋白HMGB1、RAGE、TLR2、TLR4和NF-κB在糖尿病肾病小鼠中表达增高,阻断HMGB1和RAGE、TLRs结合能够阻止糖尿病肾病发展。
英文摘要:
      ObjectiveTo investigate the relationship between the expression of key proteins in high mobility group box 1 (HMGB1)- receptor for advanced glycation end products (RAGE)/ toll-like receptor (TLRs)- nuclear factor kappa-B (NF-κB) signaling pathway and diabetic nephropathy. MethodsC57BL/6 male mice were injected with streptozotocin (STZ) to establish a diabetic nephropathy (DN) model as the DN group. The saline replacement was listed as the control group, and the insulin treatment on the basic of the DN group was classified as the treatment group. The differences in body weight, blood glucose, urinary albumin quantification and key protein levels in the HMGB1-RAGE/TLRs-NF-κB signaling pathway were compared between the three groups. In addition, mice in the DN group were injected with HMGB1 antagonist A Box, and the ratio of urinary albumin and renal tissue sections were observed before and after injection. ResultsCompared with the control group, the body weight, blood glucose and urinary albumin levels in the DN group and the treatment group were significantly increased (P<0.01). Compared with the DN group, the above indexes were significantly decreased in the treatment group (P<0.05). At each time period after the modeling was completed, the protein levels of HMGB1, RAGE, TLR4, and NF-κB in the DN group were significantly higher than those in the control group (P<0.05). The mice in the treatment group HMGB1 RAGE, TLR2, TLR4 and NF-κB protein levels were significantly higher than those of the control group (P<0.05). The mRNA levels of HMGB1, RAGE, TLR2, TLR4 and NF-κB in the DN group and the treatment group were significantly higher than those of the control group (P<0.01). Compared with the DN group in the same time, the levels of the above proteins and mRNA were significantly lower in the treatment group (P<0.05). After A Box administration, there was no significant change in histological staining of saline-treated mice (P=0.933), and the interstitial collagen precipitation in DN model mice was significantly decreased (P=0.013). ConclusionThe expression of HMGB1, RAGE, TLR2, TLR4 and NF-κB in HMGB1-RAGE/TLRs-NF-κB signaling pathway is increased in mice with Diabetic nephropathy. Blocking HMGB1, RAGE and TLRs can prevent the development of diabetic nephropathy.
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