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| 1 | Pathogenesis of alcoholic liver disease:Role of oxidative metabolism显示文摘Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases,resulting in fatty liver,alcoholic hepatitis,fibrosis/cirrhosis,and hepatocellular carcinoma(HCC).Although the pathogenesis of alcoholic liver disease(ALD)involves complex and still unclear biological processes,the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species(ROS)play a preeminent role in the clinical and pathological spectrum of ALD.Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes,leading to fat accumulation,fibrogenesis and activation of innate and adaptive immunity.Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis,decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase(AMPK)-dependent mechanism.AMPK activation by ROS modulates autophagy,which has an important role in removing lipid droplets.Acetaldehyde and aldehydes generated from lipid peroxidation induce collagensynthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells(HSCs).Furthermore,activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD.Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide(LPS)translocation by disrupting tight and adherent junctions in human colonic mucosa.Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration.In addition,alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver.Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells,and consequently alters allogenic antigen presentation.Finally,acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis,and they interfere with methylation,synthesis and repair of DNA,thereby increasing HCC susceptibility. | Elisabetta Ceni Tommaso Mello Andrea Galli | 2014 | World Journal of Gastroenterology2014，20，47： | 72 |
| 2 | 自噬在疾病中的双重作用显示文摘自噬是细胞的一种正常的生理活动,参与细胞内损伤的蛋白质和亚细胞器经溶酶体途径降解的过程。自噬可以抵御外界的不良环境,在多种疾病中起着重要作用。近年来,大量研究表明自噬在细胞新陈代谢和生理功能上有双重作用,在疾病发生的不同时期,自噬起到不同的作用。通常情况自噬可以及时的清除细胞内损伤的蛋白质,作为一种细胞的保护机制,但是自噬的持续活化,导致细胞内大量蛋白质的降解,使细胞无法维持其基本结构,最终将导致细胞坏死或凋亡。自噬、凋亡和坏死的转化,很有可能受到p53、Bcl-2、Beclin-1、ATG5、TG2及p62等信号分子调控。肝脏和心脏是维持人体生命活动的重要器官,自噬在脂肪肝、肝硬化、心肌梗塞及心脏衰竭等疾病中扮演着重要的角色。本文总结了自噬、凋亡及坏死的相互关系,自噬在疾病中的双重作用,并重点介绍自噬在肝脏和心脏疾病中的作用。 | 王旭垒 熊剑锐 赵启明 蒋维 李萍 | 2014 | 现代生物医学进展2014，14，25： | 15 |
| 3 | New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases显示文摘Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α. | Jessica A Williams Sharon Manley Wen-Xing Ding | 2014 | World Journal of Gastroenterology2014，20，36： | 10 |
| 4 | 蚕蛹油对3种不同类型肝损伤小鼠的保护作用显示文摘目的:研究蚕蛹油对3种不同类型的肝损伤小鼠的保护作用。方法:雄性ICR小鼠150只,按体质量随机分为3大组:实验a组(酒精性肝损伤组)、实验b组(免疫性肝损伤组)、实验c组(D-半乳糖胺肝损伤组)。每大组再随机分为5个小组:空白对照组、月见草油阳性对照组、肝损伤模型组及蚕蛹油低、高剂量组。灌胃7d后,除空白对照组外,各实验组分别进行如下处理:实验a组给予50%乙醇12mL/kg,建立小鼠酒精性肝损伤模型;实验b组采用尾静脉注射卡介苗(BCG)+脂多糖(LPS)诱导小鼠免疫性肝损伤;实验c组以10%D-半乳糖胺600mg/kg给各组小鼠腹腔注射,诱导小鼠D-半乳糖胺肝损伤模型。24h后测定血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性和肝组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量;观察肝脏、脾脏指数的变化。结果:蚕蛹油组肝脏指数、脾脏指数、ALT和AST的活性及肝组织中MDA、还原型GSH水平与模型组各水平相比均具有显著性差异(P<0.05),且肝脏、脾脏指数水平与ALT、AST活性及MDA、GSH含量相关性显著(P<0.05)。结论:蚕蛹油对酒精所致小鼠急性化学性肝损伤、卡介苗和脂多糖诱导的免疫性肝损伤、D-半乳糖胺所造成的小鼠肝损伤均具有明显的保护作用,且对酒精性肝损伤及BCG和LPS诱导的免疫性肝损伤保护效果优于月见草油,其机制可能与其降酶、降低脂质过氧化水平、阻止肝细胞坏死作用有关。 | 陈伟平 谢园沁 胡金鹿 | 2012 | 食品科学2012，33，15： | 10 |
| 5 | 紫心甘薯对四氯化碳、卡介苗加脂多糖诱发小鼠肝损伤的保护作用显示文摘研究紫心甘薯对四氯化碳(CCl4)、卡介苗加脂多糖(BCG+LPS)诱发小鼠肝损伤的保护作用。ICR小鼠100只,雄性,按体重随机分为两大组,每大组随机分为5个小组,连续给药12d后,除空白组外,各实验组分别进行如下处理:A组:按10mL/kg剂量腹腔注射体积分数0.1%CCl4油溶液,建立小鼠肝损伤模型;B组:采用尾静脉注射BCG+LPS诱导小鼠免疫性肝损伤。12h后测定血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性和肝组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量;观察肝脏、脾脏系数的变化。紫心甘薯组各组肝、脾指数、谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性和肝组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)水平与模型对照组各水平相比均具有显著性差异(P<0.05),且肝、脾指数水平与ALT、AST、MDA、GSH含量相关性显著(P<0.05)。说明紫心甘薯对CCl4所致小鼠急性化学性肝损伤、BCG+LPS诱导的免疫性肝损伤均具有显著的保护作用,且对CCl4所致小鼠急性化学性肝损伤、卡介苗和脂多糖诱导的免疫性肝损伤保护效果优于联苯双酯,其机制可能与其降酶、降低脂质过氧化水平、阻止肝细胞坏死作用有关。 | 陈伟平 谢园沁 胡金鹿 马晓雯 王珍姝 | 2011 | 食品与生物技术学报2011，30，6： | 9 |
| 6 | Beclin-1- mediated autophagy may be involved in the elderly cognitive and affective disorders in streptozotocininduced diabetic mice显示文摘Background:Diabetes is the most common metabolic disease with many chronic complications,and cognitive disorders are one of the common complications in patients with diabetes.Previous studies have showed that autophagy played important roles in the progression of metabolic syndrome,diabetes and other diseases.So we investigated whether aged diabetic mice are prone to be associated with the cognitive and affective disorders and whether Beclin-1-mediated autophagy might be involved in thepahological process.Methods:High-fat diet/streptozotocin(STZ)injection-induced diabetic C57 mice were adopted in this study.Cognitive disorders were detected by Morris water maze and fear conditional test.Affective disorders were detected by tail suspension test and forced swimming test.Magnetic resonance imaging was applied to observe changes of morphology and metabolism in the brain.The 18 F-fluorodeoxyglucose positron emission tomography(FDG-PET)was used to assess metabolism changes in the brain of aged diabetic mice.Autophagy were evaluated by Beclin-1,LC3II/I and P62,which were detected by western blot analysis and observed by electron microscopy.Results:1.Compared with control group,diabetes mice showed significantly decreasing abilities in spatial memory and conditioned fear memory(all P<0.05),and increasing tendency of depression(P<0.05).2.MRI showed that the majority of elderly diabetic mice were associated with multiple cerebral small vessel disease.Some even showed hippocampal atrophy,ventricular dilatation and leukoaraiosis.3.FDG-PET-CT discovered that the glucose metabolism in the amygdala and hippocampus was significantly decreased compared with normal aged mice(P<0.05).4.Electron microscopy found that,although autophagy bodies was not widespread,and there was no significant difference between the two groups,yet compared with normal aged mice,apparent cell edema,myelinated tow reduction and intracellular lipofuscin augmentation existed in elderly diabetic mice brain.5.The level of p62 was increased in the STZ-induced diabetic mice hippocampus and striatum,and beclin1 protein expression were significantly decreased in diabetic mice hippocampus compared with normal aged mice(P<0.05).There was a upward trend of the ratio of LC3II/I in hippocampus,cortex and striatum,but no statistically difference between the two groups.Conclusion:Compared with normal aged mice,diabetic aged mice were apt to cerebral small vessel disease and associated with cognitive and affective disorders,which may be related to the significantly reduced glucose metabolism in hippocampus and amygdala.Beclin1 mediated autophagy in hippocampus probably played an important role in cognitive and affective disorders of STZ-induced aged diabetic mice. | Zhu-Fei Guan Xiu-Ling Zhou Xiao-Ming Zhang Yu Zhang Yan-Mei Wang Qi-Lin Guo Gang Ji Guo-Feng Wu Na-Na Wang Hao Yang Zhong-Yu Yu Hou-Guang Zhou Jing-Chun Guo Ying-Chao Liu | 2016 | Translational Neurodegeneration2016，5，1： | 8 |
| 7 | 自噬在化学物所致肝细胞损伤中的修复作用显示文摘自噬是真核细胞普遍存在的一种溶酶体降解途径,利用溶酶体水解酶降解细胞内组分和亚细胞器,降解产物为氨基酸和脂肪酸,用于补充能量,合成新的蛋白质和亚细胞器,维持细胞正常功能。肝脏是机体新陈代谢的重要器官,自噬对于维持肝细胞正常功能,修复肝损伤具有重要意义。本文从降解错误折叠的蛋白质,清除受损的亚细胞器,调节脂代谢平衡和抑制肝细胞癌变等方面对自噬在化学物所致的肝细胞损伤中的修复作用进行了综述。 | 谢颖 钟才高 | 2013 | 卫生研究2013，42，6： | 1 |
| 8 | 自噬与脂肪性肝病显示文摘自噬( autophagy)是真核细胞所特有的生命现象,是细胞利用溶酶体降解自身受损的细胞器如线粒体和大分子物质的过程,自噬参与细胞废物的清除、结构的重建、生长与分化,是细胞对不良刺激的一种生存防御机制。近年来,自噬与肝脏疾病的关系已成为医学研究的热点,自噬与肝脏缺血性疾病、肝脏肿瘤的发生、发展,以及与某些先天代谢性肝脏疾病都有着密不可分的关系[1]。同时,自噬在脂肪性肝病的发生发展中也起到了举足轻重的作用。 | 陈洁 陈东风 苏立稳 | 2014 | 中西医结合肝病杂志2014，24，5： | 1 |
| 9 | Autophagy in liver diseases: A matter of what to remove and whether to keep显示文摘1.Introduction There are three types of autophagy,macroautophagy,microautophagy and chaperon-mediated autophagy.Macroautophagy is the largest in terms of the scale,and often briefly referred to as autophagy as here.In recent years,researches in the field of autophagy have become such a strong trend that many new findings have been made that advance not only the understanding of the biology of autophagy. | Xiao-Ming Yin | 2018 | Liver Research2018，2，3： | 0 |
| 10 | 自噬与脂代谢显示文摘自噬是细胞清除受损或多余的蛋白质和细胞器的降解过程。最近研究发现,脂滴也是自噬过程的底物之一。在营养状态改变时,自噬能够根据机体需要增加或减少对脂滴的降解,从而起到调节脂代谢的作用。此外,自噬在脂滴形成及脂肪组织分化过程中也发挥重要作用。在细胞水平以自噬为靶点是治疗肥胖、胰岛素抵抗和2型糖尿病的新途径。 | 邓玉杰 杨颖 | 2011 | 国际内分泌代谢杂志2011，31，5： | 0 |
| 11 | Voacanga grandifolia(Miq.)Rolfe protects against alcohol-induced liver toxicity in rats显示文摘Objective:To evaluate the ethanol extract of Voacanga grandifolia for hepatoprotective and antioxidant potential against ethanol-induced liver toxicity in rats.Methods:Sprague-Dawley rats were administered ethanol(7 g/kg)and then treated with 100 and 200 mg/kg of Voacanga grandifolia extract.The phytochemical constituents and antioxidant potential of Voacanga grandifolia extract were evaluated by GC-MS and in vitro antioxidant assays.Biochemical indicators for liver damage and pro-apoptotic and antiapoptotic gene expression were determined using biochemical kits,ELISA,and qRT-PCR,respectively.Additionally,histopathological study of the liver was performed.Results:GC-MS identified propanoic acid,meso-erythritol,D-pinitol,myo-inositol,and hexadecanoic acid in Voacanga grandifolia extract.Voacanga grandifolia extract(100 and 200 mg/kg)increased the concentration of enzymatic antioxidants while diminishing the levels of inflammatory cytokines and biochemical indicators.qRT-PCR assay showed that Voacanga grandifolia extracts upregulated antiapoptotic gene expression while downregulating pro-apoptotic gene expression.Furthermore,the plant extract improved the hepatic architecture of ethanol-intoxicated rats.Conclusions:Voacanga grandifolia extract demonstrates hepatoprotective activity against alcohol-induced liver injury in rats and could be a potential hepatoprotective agent. | Lal Chand Pal Shivankar Agrawal Arti Gautam | 2022 | Asian Pacific Journal of Tropical Biomedicine2022，12，12： | 0 |
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