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Hepatology: 肝功能不全患者缺乏肝再生蛋白会促进非酒精性脂肪性肝炎和纤维化的发生

2020-11-10 网络 网络

肝再生(ALR)蛋白(由生长因子ERV1同源基因编码)的增强剂在肝脏中高表达,主要在肝细胞中,并在细胞质,细胞核和线粒体中发现。

      肝再生(ALR)蛋白(由生长因子ERV1同源基因编码)的增强剂在肝脏中高表达,主要在肝细胞中,并在细胞质,细胞核和线粒体中发现。肝细胞分泌ALR,并且是血清中的主要来源。ALR的线粒体功能至关重要,因为它的耗竭会导致三磷酸腺苷(ATP)迅速丢失,从而导致细胞死亡。ALR在小鼠中的整体敲除具有胚胎致死性,表明其在胚胎发育中至关重要。肝细胞特异性敲除ALR的小鼠在出生时正常,但会出现过度的脂肪变性,线粒体功能障碍和变性,并迅速死亡。非酒精性脂肪肝疾病(NAFLD)的发病率增加是全球性的挑战。NAFLD中有44%的患者会发展为非酒精性脂肪性肝炎(NASH),而具有明显NASH的受试者会发展为肝硬化和肝细胞癌。本项研究假设ALR缺乏可能是NASH及其在基础疾病未被诊断的受试者中无声发展为纤维化/肝硬化的重要诱因。

 

      高脂/高碳水化合物(HF / HC)喂养降低了所有小鼠的ALR表达。当用HF / HC饮食进行代谢攻击时,ALR小鼠比WT小鼠体重增加更明显和脂肪变性也更严重。ALR敲除小鼠的体重最少,脂肪变性最少。这些发现与甘油三酯和胆固醇的相应增加以及肉碱棕榈酰转移酶1a,固醇调节元件结合蛋白,乙酰辅酶A羧化酶和脂肪酸合酶的表达改变相一致。所有用HF / HC喂养的小鼠均出现胰岛素抵抗,在ALR敲除小鼠中幅度较小。HF / HC喂养的ALR小鼠比WT或ALR敲除小鼠对葡萄糖攻击的抵抗力更高。产生肿瘤坏死因子的频率,产生白介素6(IL6)的频率,产生IL17的细胞在ALR敲除小鼠中比ALR鼠中更大,在WT小鼠中最低。HF / HC喂养在ALR敲除小鼠中并未增加其数量,除IL17细胞外,ALR小鼠体重的增加大于野生型小鼠。HF / HC喂养仅在野生型小鼠中降低调节性T细胞频率。HF / HC喂养的ALR小鼠但未出现肝脏纤维化。ALR敲除小鼠发展为肝硬化的可能性更高。HF / HC喂养的ALR缺乏小鼠的白色脂肪组织发生强烈的炎症反应,表明与肝脏出现了双向相互作用。NASH肝硬化患者的肝和血清ALR水平显着降低。NASH患者的血清ALR也显着降低。

 

 

       由此,研究人员得出一个结论:肝ALR缺乏可能是侵袭性NAFLD进展的关键诱发因素。

 

 

原始出处:

Sudhir Kumar. Et al. Hepatic Deficiency of Augmenter of Liver Regeneration Predisposes to Nonalcoholic Steatohepatitis and Fibrosis. Hepatology.2020.

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    2020-12-01 qjddjq
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    2020-11-12 gwc384

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牙周病是一种常见的口腔慢性炎症疾病,包括牙周炎,坏死性牙周炎和作为系统性疾病表现的牙周炎。多种全身性疾病与牙周病的进展和严重程度有关。流行病学证据表明,肝脏受损患者发生牙周病的风险较高。

肝病研发企业新通药物完成Pre-IPO融资,预计明年在科创板上市

近日,国内肝病新药研发企业——西安新通药物研究有限公司(以下简称“新通药物”)宣布完成Pre-IPO轮逾亿元人民币融资,本轮融资由北拓资本担任专项财务顾

Aliment Pharmacol Ther :多喝咖啡,就可以降低近一半的肝病死亡率?

肝病是导致人类健康的杀手之一,据统计,全球每年约超过100万人死于肝硬化,约七十四万人因肝硬化引发的肝癌死亡,占每年总死亡人数的3.5%以上。

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