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首页> 外文期刊>Comparative and functional genomics >Lingguizhugan Decoction Protects against High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress and Activating Cholesterol Secretion
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Lingguizhugan Decoction Protects against High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress and Activating Cholesterol Secretion

机译:灵桂竹肝汤可减轻氧化应激和激活胆固醇分泌,从而预防高脂饮食引起的非酒精性脂肪性肝病

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Background. Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of liver transplantation. Lingguizhugan decoction (LGZG), a classical Chinese herbal formula, has beneficial effects on NAFLD animal models. Our study examined the impact of LGZG on hepatic global transcriptome of high-fat-diet-induced NAFLD rats. Methods. Three groups of Wistar rats were included normal, NAFLD model, and LGZG-treated NAFLD groups. Four weeks for the treatment, liver tissues were harvested for RNA sequencing. Differentially expressed genes (DEGs) and enriched pathways were detected on hepatic global transcriptome profile. Real-time PCR validated the regulatory patterns of LGZG on NAFLD rats. Results. DEGs between the NAFLD model and normal groups indicated the elevated peroxisome proliferator-activated receptor (PPAR) and hedgehog signaling pathways in NAFLD rats. In bile secretion pathway, genes involved in cholesterol secretion were activated by LGZG treatment. Increased expression of antioxidant OSIGN1 and decreased expression of genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG treatment on these oxidative stress-related genes were confirmed by real-time PCR. Conclusion. Our study revealed a “two-hits-targeting” mechanism of LGZG in the treatment for NAFLD alleviating oxidative stress and activating cholesterol secretion.
机译:背景。非酒精性脂肪肝疾病(NAFLD)已成为肝脏移植的主要原因。灵桂竹肝汤(LGZG)是一种经典的中草药配方,对NAFLD动物模型具有有益的作用。我们的研究检查了LGZG对高脂饮食诱导的NAFLD大鼠肝脏整体转录组的影响。方法。三组Wistar大鼠包括正常,NAFLD模型和LGZG治疗的NAFLD组。处理四周,收获肝组织用于RNA测序。在肝整体转录组图谱上检测到差异表达基因(DEG)和丰富的途径。实时PCR验证了LGZG对NAFLD大鼠的调控模式。结果。 NAFLD模型与正常组之间的DEGs表明,NAFLD大鼠中过氧化物酶体增殖物激活受体(PPAR)和刺猬信号通路升高。在胆汁分泌途径中,参与LGZG处理的胆固醇分泌基因被激活。在用LGZG治疗的NAFLD大鼠中观察到了抗氧化剂OSIGN1的表达增加和诱导氧化应激和炎症的基因(AHR,IRF2BP2和RASGEF1B)的表达减少。实时荧光定量PCR证实了LGZG处理这些氧化应激相关基因的调控模式。结论。我们的研究揭示了LGZG在NAFLD缓解氧化应激和激活胆固醇分泌的治疗中的“两命中”机制。

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