Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol.
Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol.
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DOI：
10.1016/j.ajpath.2019.05.011
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发表时间：
2019-09
期刊：
影响因子：
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通讯作者：
Shengmin Yan;Jun Zhou;Xiaoyun Chen;Z. Dong;Xiao-Ming Yin
中科院分区：
文献类型：
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作者：
Shengmin Yan;Jun Zhou;Xiaoyun Chen;Z. Dong;Xiao-Ming Yin
酒精性脂肪肝常并发其他病理性损害，如病毒感染或高脂肪饮食。自噬在肝脏中起稳态作用，但可被酒精、高脂肪饮食或病毒感染破坏，进而影响由这些病因引起的疾病过程。为了了解自噬调节对酒精性肝损伤的全面影响，研究人员在急性暴饮或慢性加暴饮治疗后，研究了几种具有不同程度功能改变的自噬缺陷遗传模型。在诱导atg7缺失后不久，以两种方式给予酒精并诱导肝脏特异性atg7缺失的小鼠肝损伤升高，表明自噬的保护作用。在胚胎中缺失肝蛋白7的构成型肝蛋白7缺陷小鼠更容易受到慢性加暴的影响，但对急性酒精治疗没有影响。肝catg5缺陷小鼠，在胚胎中缺失了hatg5，更容易受到急性酒精治疗，但肝损伤出乎意料地在慢性+暴饮方案中得到改善。长期的自噬不足可能使肝脏对酒精治疗的反应复杂化，部分原因可能是内源性肝损伤。因此，自噬缺乏与酒精性肝损伤之间关系的复杂性可能受到自噬功能障碍发生的时间、受影响的确切自噬基因以及酒精治疗方案的影响。
Alcoholic fatty liver disease is often complicated by other pathologic insults, such as viral infection or high-fat diet. Autophagy plays a homeostatic role in the liver but can be compromised by alcohol, high-fat diet, or viral infection, which in turn affects the disease process caused by these etiologies. To understand the full impact of autophagy modulation on alcohol-induced liver injury, several genetic models of autophagy deficiency, which have different levels of functional alterations, were examined after acute binge or chronic-plus-binge treatment. Mice given alcohol with either mode and induced with deficiency in liver-specificAtg7shortly after the induction ofAtg7deletion had elevated liver injury, indicating the protective role of autophagy. Constitutive hepaticAtg7–deficient mice, in whichAtg7was deleted in embryos, were more susceptible with chronic-plus-binge but not with acute alcohol treatment. Constitutive hepaticAtg5–deficient mice, in whichAtg5was deleted in embryos, were more susceptible with acute alcohol treatment, but liver injury was unexpectedly improved with the chronic-plus-binge regimen. A prolonged autophagy deficiency may complicate the hepatic response to alcohol treatment, likely in part due to endogenous liver injury. The complexity of the relationship between autophagy deficiency and alcohol-induced liver injury can thus be affected by the timing of autophagy dysfunction, the exact autophagy gene being affected, and the alcohol treatment regimen.