Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice
Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice
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Recql5 预防脂多糖/D-半乳糖胺诱导的小鼠肝损伤
DOI：
10.3748/wjg.v21.i36.10375
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发表时间：
2015-09-28
影响因子：
4.3
通讯作者：
Lu, Xin-Cheng
中科院分区：
文献类型：
--
作者：
Liao, Wan-Qin;Qi, Ya-Lei;Lu, Xin-Cheng
目的：目的：探讨Recql 5缺陷对脂多糖/D-氨基半乳糖（LPS/D-Gal）诱导的小鼠肝损伤的影响。肝细胞凋亡定量转移酶dUTP缺口末端标记法和蛋白质印迹分析裂解caspase-3。用定量逆转录-PCR分析肝脏炎性趋化因子和细胞色素P450的表达。通过髓过氧化物酶活性评价神经元浸润。通过蛋白质印迹法测定ERK、JNK、p65和H2 A. X的表达和磷酸化。通过测量丙二醛的产生和一氧化氮合酶，超氧化物歧化酶，谷胱甘肽过氧化物酶，过氧化氢酶，谷胱甘肽还原酶activity.Results：LPS/D-Gal暴露后，Recql 5缺陷小鼠表现出增强的肝损伤，更严重的肝出血，更高的血清天冬氨酸转氨酶和丙氨酸转氨酶水平，和较低的生存率证明。与WT小鼠相比，Recql 5缺陷型小鼠显示凋亡肝细胞数量增加和裂解的半胱天冬酶-3水平更高。Recql 5缺陷型小鼠表现出增加的DNA损伤，如通过增加的γ-H2 A所证明的。X层在基因敲除小鼠中，炎性细胞因子水平、中性粒细胞浸润和ERK磷酸化也显著增加。此外，Recql 5缺陷小鼠表现出增加的丙二醛产生和升高的诱导型一氧化氮合酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和谷胱甘肽还原酶活性，表明氧化应激增强。结论：Recql 5通过抑制肝细胞凋亡和氧化应激，调节CYP 450的表达，对LPS/D-Gal诱导的肝损伤具有保护作用。
AIM: To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal).METHODS: Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity.RESULTS: Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased gamma-H2A. X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficicent mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment.CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.