AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containi...AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF(Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure(ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or AdHGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1(HMGB1), endotoxin, tumour necrosis factor(TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGFHIL-6-treated rats with ACLF. Likewise, reduced hepaticdamage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGFHIL-6 treatment groups, more predominantly in the latter group.CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.展开更多
基金Supported by Natural Science Foundation of Chongqing,No.cstc2012jj A10052Young High-End Medical Reserve Personnel Training Plan Foundation of Chongqing,China
文摘AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF(Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure(ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or AdHGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1(HMGB1), endotoxin, tumour necrosis factor(TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGFHIL-6-treated rats with ACLF. Likewise, reduced hepaticdamage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGFHIL-6 treatment groups, more predominantly in the latter group.CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.
文摘目的检测子痫前期孕妇血清中人端粒酶反转录酶(human telomerase reverse transcriptase,hTERT)、沉默信息调节因子6(silent information regulator 6,Sirt6)表达,并探究hTERT,Sirt6水平表达与疾病严重程度及妊娠结局评估中的价值。方法选取2018年1月~2022年12月在陕西省人民医院进行诊治的300例子痫前期孕妇作为子痫前期组,孕妇均符合《妊娠期高血压疾病诊治指南(2015)》中子痫前期诊断标准,选取同时期孕检的300例健康孕妇为对照组,根据病情严重程度将子痫前期组分为轻症子痫前期组(n=180)和重症子痫前期组(n=120),根据是否发生不良妊娠结局将子痫前期组分为正常妊娠组(n=165)和不良妊娠组(n=135)。酶联免疫吸附实验(enzyme-linked immunosorbnent assay,ELISA)法检测血清中hTERT和Sirt6水平,Spearman相关性分析血清中hTERT和Sirt6水平与子痫前期孕妇病情严重程度的相关性,利用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清hTERT和Sirt6水平在子痫前期诊断及妊娠结局预测中的价值。结果与对照组比较,子痫前期组血清hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml),Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)水平降低,差异具有统计学意义(t=12.334,11.114,均P<0.001)。与轻症子痫前期组比较,重症子痫前期组孕妇血清hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml),Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)水平降低,差异具有统计学意义(t=9.142,10.469,均P<0.001)。与正常妊娠组比较,不良妊娠组子痫前期孕妇血清中hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml),Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)水平降低,差异具有统计学意义(t=11.639,10.878,均P<0.001)。Spearman相关性分析显示,血清hTERT,Sirt6水平与子痫前期孕妇疾病严重程度均呈负相关(r=-0.562,-0.604,均P<0.001)。ROC曲线分析结果显示,血清hTERT,Sirt6诊断子痫前期的曲线下面积(95%置信区间)[AUC(95%CI)]分别为0.711(0.673~0.747),0.727(0.689~0.762),两者联合诊断子痫前期的AUC(95%CI)为0.788(0.753~0.820),高于两者单独诊断(Z=2.719,2.154,P=0.007,0.031);血清hTERT,Sirt6预测子痫前期不良妊娠结局的AUC(95%CI)分别为0.786(0.735~0.831),0.783(0.732~0.829),两者联合预测子痫前期不良妊娠结局的AUC(95%CI)为0.849(0.804~0.888),高于两者单独预测(Z=1.855,1.861,P=0.032,0.031)。结论hTERT和Sirt6在子痫前期孕妇血清中水平较低,与子痫前期孕妇疾病严重程度均呈负相关,并对妊娠结局具有一定的评估价值。