目的观察轻中型颅脑损伤继发轻度认知功能障碍(MCI)后血清中高迁移率族蛋白B1(highmobility group box-1,HMGB1)和Toll样受体2(toll like receptor-2,TLR2)的表达情况并探讨其临床意义。方法选择郑州大学第五附属医院神经外科自2016年1...目的观察轻中型颅脑损伤继发轻度认知功能障碍(MCI)后血清中高迁移率族蛋白B1(highmobility group box-1,HMGB1)和Toll样受体2(toll like receptor-2,TLR2)的表达情况并探讨其临床意义。方法选择郑州大学第五附属医院神经外科自2016年1月至2017年12月收治的格拉斯哥昏迷评分(GCS)9~15分的轻中型颅脑损伤患者115例为颅脑损伤组,同期于门诊体检的20例符合条件的健康者作为健康组。应用双抗体夹心酶联免疫吸附实验(ELISA)测定两组血清中HMGB1、TLR2水平;分析各组血清中HMGB1和TLR2的表达。结果 3个月后,轻型颅脑损伤组和中型颅脑损伤组与健康组比较,其血清HMGB1、TLR2明显增高(q=42.442,24.264;均P<0.05);中型颅脑损伤组血清HMGB1水平比轻型颅脑损伤组比明显增高(q=17.122,P<0.05),TLR2水平无明显差异(q=2.416,P>0.05)。多组间血清中HMGB1和TLR2水平比较有统计学意义(F=520.008,169.249;均P<0.05);进一步分析,轻型颅脑损伤不伴MCI组和中型颅脑损伤不伴MCI组比健康组血清中HMGB1和TLR2水平高(q=33.252,24.126;均P<0.05),轻型颅脑损伤不伴MCI组和中型颅脑损伤不伴MCI组之间HMGB1和TLR2水平无明显差异(q=2.422,P>0.05);轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比健康组血清中HMGB1和TLR2水平高(q=48.374,44.522;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比轻型颅脑损伤不伴MCI组血清中HMGB1和TLR2水平高(q=28.674,21.351;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比中型颅脑损伤不伴MCI组血清中HMGB1和TLR2水平高(q=19.974,16.465;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组之间HMGB1和TLR2水平无明显差异(q=3.584,P>0.05);颅脑损伤伴MCI患者血清中TLR2和HMGB1的水平呈正相关[Y=0.372X-0.408(r=0.874,P<0.01)];颅脑损伤不伴MCI患者血清中TLR2和HMGB1无明显相关性[Y=0.285X+0.038(r=0.459,P=0.064)]。结论轻中型颅脑损伤患者血清中高表达的HMGB1展开更多
The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphologi...The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.展开更多
目的癫痫脑内可大量释放高迁移率族蛋白1(high mobility group box protein 1,HMGB1),但针对HMGB1与癫痫脑内血管内皮细胞过表达的耐药蛋白P-糖蛋白(P-glycoprotein,P-gp)关系的研究甚少。文中探讨HMGB1对体外培养的小鼠脑微血管内皮细...目的癫痫脑内可大量释放高迁移率族蛋白1(high mobility group box protein 1,HMGB1),但针对HMGB1与癫痫脑内血管内皮细胞过表达的耐药蛋白P-糖蛋白(P-glycoprotein,P-gp)关系的研究甚少。文中探讨HMGB1对体外培养的小鼠脑微血管内皮细胞P-gp表达的影响。方法体外培养永生化小鼠脑微血管内皮细胞株b End.3,分为不同浓度HMGB1组(10、100、500、1000 ng/m L HMGB1处理b End.3细胞8 h);不同时间HMGB1处理组(以100 ng/m L HMGB1处理b End.3细胞4、8、16、24、32 h);对照组(给予等量正常培养基)。采用实时定量PCR检测b End.3细胞中P-gp编码基因多药耐药基因1a(mdr1a)mRNA表达水平,免疫印迹法、免疫细胞化学法检测P-gp蛋白表达水平。结果 q PCR结果显示:10、100、500、1000ng/m L HMGB1组mdr1a mRNA表达量分别为1.646±0.176、1.777±0.135、1.617±0.043和1.398±0.182,较对照组(1.030±0.284)明显升高(P<0.05)。HMGB1处理4、8、16、24、32 h组mdr1a mRNA表达量分别为2.655±0.112、2.168±0.212、1.823±0.232、1.418±0.376和1.445±0.123,较对照组(1.010±0.164)明显升高(P<0.05)。免疫印迹法结果显示:与对照组比较,各浓度组P-gp蛋白表达水平均增高(P<0.05),HMGB1处理8、16 h组P-gp蛋白表达增高(P<0.05)。免疫细胞化学染色结果显示:100 ng/m L HMGB1处理16 h后P-gp蛋白表达灰度值(110.843±4.036)较对照组(160.303±2.193)明显减少(P<0.01)。结论 HMGB1能够上调小鼠脑微血管内皮细胞耐药蛋白P-gp和其编码基因mdr1a表达,可能与中枢神经系统疾病尤其是癫痫的耐药相关。展开更多
文摘目的观察轻中型颅脑损伤继发轻度认知功能障碍(MCI)后血清中高迁移率族蛋白B1(highmobility group box-1,HMGB1)和Toll样受体2(toll like receptor-2,TLR2)的表达情况并探讨其临床意义。方法选择郑州大学第五附属医院神经外科自2016年1月至2017年12月收治的格拉斯哥昏迷评分(GCS)9~15分的轻中型颅脑损伤患者115例为颅脑损伤组,同期于门诊体检的20例符合条件的健康者作为健康组。应用双抗体夹心酶联免疫吸附实验(ELISA)测定两组血清中HMGB1、TLR2水平;分析各组血清中HMGB1和TLR2的表达。结果 3个月后,轻型颅脑损伤组和中型颅脑损伤组与健康组比较,其血清HMGB1、TLR2明显增高(q=42.442,24.264;均P<0.05);中型颅脑损伤组血清HMGB1水平比轻型颅脑损伤组比明显增高(q=17.122,P<0.05),TLR2水平无明显差异(q=2.416,P>0.05)。多组间血清中HMGB1和TLR2水平比较有统计学意义(F=520.008,169.249;均P<0.05);进一步分析,轻型颅脑损伤不伴MCI组和中型颅脑损伤不伴MCI组比健康组血清中HMGB1和TLR2水平高(q=33.252,24.126;均P<0.05),轻型颅脑损伤不伴MCI组和中型颅脑损伤不伴MCI组之间HMGB1和TLR2水平无明显差异(q=2.422,P>0.05);轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比健康组血清中HMGB1和TLR2水平高(q=48.374,44.522;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比轻型颅脑损伤不伴MCI组血清中HMGB1和TLR2水平高(q=28.674,21.351;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组比中型颅脑损伤不伴MCI组血清中HMGB1和TLR2水平高(q=19.974,16.465;均P<0.05),轻型颅脑损伤伴MCI组和中型颅脑损伤伴MCI组之间HMGB1和TLR2水平无明显差异(q=3.584,P>0.05);颅脑损伤伴MCI患者血清中TLR2和HMGB1的水平呈正相关[Y=0.372X-0.408(r=0.874,P<0.01)];颅脑损伤不伴MCI患者血清中TLR2和HMGB1无明显相关性[Y=0.285X+0.038(r=0.459,P=0.064)]。结论轻中型颅脑损伤患者血清中高表达的HMGB1
基金supported by the National Natural Science Foundation of China (Grant No. 81700723)Research Project of Jiangsu 333 Engineering (Grant No. BRA2016232)Research Project of Jiangsu Provincial Commission of Health and Family Planning (Grant No. F201549/H201667)
文摘The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.
