AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated th...Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.展开更多
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
AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepati...AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepatic fibrosis in rats was induced through serial subcutaneous injections of dimethylnitrosamine,and expression of HMGB1 was detected by immunohistochemistry.HMGB1 siRNAs were developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000.HMGB1 expression was evaluated by real-time polymerase chain reaction (PCR) and Western blotting analysis.Expression of α-smooth muscle actin (α-SMA) and collagen typesⅠand Ⅲ was evaluated by real-time PCR.Cell proliferation and the cell cycle were determined using the methyl thiazolyl tetrazolium method.Finally,collagen content in HSC supernatant was evaluated by an enzyme-linked immunosorbent assay.RESULTS:The results showed that HMGB1 was upregulated during liver fibrosis and that its expression was closely correlated with the deposition of collagen.siRNA molecules were successfully transfected into HSCs and induced inhibition of HMGB1 expression in a time-dependent manner.Moreover,HMGB1 siRNA treatment inhibited synthesis of α-SMA and collagen types Ⅰ and Ⅲ in transfected HSCs.CONCLUSION:This study suggests a significant functional role for HMGB1 in the development of liver fibrosis.It also demonstrates that downregulation of HMGB1 expression might be a potential strategy to treat liver fibrosis.展开更多
基金Supported by Samsung Biomedical Research Institute grant,No.SBRI C-A8-219-1
文摘AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
基金This work was supported by the grants from the National Natural Science Foundation of China （No.30471675, No.30672041 and No.30725039） the National Natural Science Foundation of Shaanxi Province （No.2004KI7-GI5） and the National Natural Science Foundation of PLA （No.06G086）.We are grateful to Drs. LI Qing and HUI Yan-ping （Department of Pathology, Fourth Military Medical University） for assisting in histopathological analysis+1 种基金 to Dr. SHANG Lei （Department of Health Statistics, Fourth Military Medical University） for his help in the statistics analysis to Dr. LIU Shan-lu （Department of Microbiology and Immunology, McGill University） for his insightful comments.
文摘Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.
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 Select and Train Outstanding Young Teach-ers Foundation of Shanghai,No.jdy08086WUJieping Experimental Diagnosis of Liver Disease Medical Foundation,No.LDWMF-SY-2011B009
文摘AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepatic fibrosis in rats was induced through serial subcutaneous injections of dimethylnitrosamine,and expression of HMGB1 was detected by immunohistochemistry.HMGB1 siRNAs were developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000.HMGB1 expression was evaluated by real-time polymerase chain reaction (PCR) and Western blotting analysis.Expression of α-smooth muscle actin (α-SMA) and collagen typesⅠand Ⅲ was evaluated by real-time PCR.Cell proliferation and the cell cycle were determined using the methyl thiazolyl tetrazolium method.Finally,collagen content in HSC supernatant was evaluated by an enzyme-linked immunosorbent assay.RESULTS:The results showed that HMGB1 was upregulated during liver fibrosis and that its expression was closely correlated with the deposition of collagen.siRNA molecules were successfully transfected into HSCs and induced inhibition of HMGB1 expression in a time-dependent manner.Moreover,HMGB1 siRNA treatment inhibited synthesis of α-SMA and collagen types Ⅰ and Ⅲ in transfected HSCs.CONCLUSION:This study suggests a significant functional role for HMGB1 in the development of liver fibrosis.It also demonstrates that downregulation of HMGB1 expression might be a potential strategy to treat liver fibrosis.
