Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury

Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkB, IL-1β, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as a1-antitrypsin (a1-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.

Oxidative stress:New insights on the association of nonalcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.

N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis

AIM: To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH). METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 8) was free accessed to regular dry rat chow (RC) for 6 wk. Group 2 (NASH, n = 8) was fed with 100% fat diet for 6 wk. Group 3 (NASH + NAC20, n = 9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study. RESULTS: The levels of total glutathione (GSH) and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7 ± 93.2 vs 1337.5 ± 31.5 μmol/L and MDA; 209.9± 43.9 vs 3.8 ±1.7 μmol/g protein, respectively, P < 0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. NAC treatment improved the level of GSH (1394.8 ± 81.2 μmol/L, P < 0.05), it did not affect MDA (150.1 ± 27.0 μmol/g protein), but led to a decrease in fat deposition and necroinflammation. CONCLUSION: NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.

Pathogenesis of alcoholic hepatitis:Role of inflammatory signaling and oxidative stress

Inflammatory signaling and oxidative stress are two major components in the pathogenesis of alcoholic he-patitis.Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in the production of inflammatory and immunogenic mediators such as tumor necrosis factor-alpha(TNF-α) and interferons.Chronic consumption of alcohol causes priming of this process in which there is enhanced production of cytokines,interferon,interleukins,and TNF-α.Oxidative stress,genetic predisposition,and the unfolded protein response are other contributory mechanisms.Novel therapies aimed at these pathways may prevent,decrease,or delay the complications of alcoholic hepatitis.

Is It Workplace Stress a Trigger for Alcohol and Drug Abuse?

Those workers most vulnerable to pressure tend to suffer from scarce social and personal resources with which to respond adaptively to stress. In this case, the effects of psychoactive substances may exceed the stressed worker’s positive expectations. Thus, the aim is to analyze the scientific evidence on the relationship between drug abuse and workplace stress, based on an integrative review of the literature. Data were collected in February 2016 from the databases of the Virtual Health Library and PubMed. The final sample of 16 articles was divided into two categories: alcohol and drugs abuse in professions with high degree of psychosocial hazards and risks, and alcohol and drugs abuse for workplace stress in other professions. A relationship between precarious conditions, the nature of the work and its influence on drug abuse could be seen. However, other variables may strengthen psychoactive drug use as a coping strategy for stress.

Influence of Early Life Stress on Alcohol and Crack Dependents

Background: Early life stress is a significant public health problem associated with increased rates of psychiatric disorders, especially those related to drug abuse. Objective: To identify the prevalence of early life stress in drug users, to compare the intensity of trauma in alcohol and crack users, and to relate the power of injury to the severity of drug dependence. Method: Cross-sectional analytical study with a sample of 105 alcohol and crack users treated by an outpatient service. The instruments for data collection were sociodemographic data questionnaire, the Mini-International Neuropsychiatric Interview, and the Severity of Dependence Scale. The categorical variables association was analyzed using the Chi-squared test, considering p Results: High prevalence of early stress and severity of dependence were identified, with higher rates among crack users. The early stress revealed in the Alcohol group high rates of emotional (88.7%) and physical (94.3%) neglect and in the Crack group significant frequency of physical (61.5%) emotional abuse (51.9%), sexual (46.2%), and emotional (78.8%) and physical (90.4%) neglect. Crack users are 2.6 times more likely to have been emotionally abused, and 2.1 times more likely to have been sexually abused during childhood when compared to the alcohol group. Conclusion: Early stress was prevalent with significant intensity in drug users, and evaluation of this problem is essential for a better understanding of these disorders.

Therapeutic Effects of"Soothing the Liver Method"on Stress-related Non-alcoholic Fatty Liver on Neuroendocrine-metabolic Level

OBJECTIVE: To study the therapeutic effects of "soothing the liver method" on stress-related non-alcoholic fatty liver and its treatment mechanism on neuroendocrine-metabolic level. METHODS: The animal model of stress-related nonalcoholic fatty liver which is more in line with the modern social and clinical conditions was established by the method of chronic restraint compound high-fat feed. AST and ALT were detected by automatic biochemical analyzer. Serum cortisol and TNF-a were detected by radioimmunoassay. The relative expression of Nr3 c1 mRNA was detected by real-time quantitative PCR. RESULTS: Compared with the blank group, the scores of open field test, Nr3 c1 mRNA decreased, and AST, ALT, FFA were significantly increased in model group. Compared with model group, the open field test scores, Nr3 c1 mRNA increased,and Cor, AST, FFA, LDL, TNF-a, were significantly decreased in SNS group. CONCLUSIONS: "Soothing the liver method" can exert its therapeutic effect on stress-related non-alcoholic fatty liver on neuroendocrine-metabolic level.

清热祛浊胶囊对非酒精性脂肪肝炎小鼠NF-κB/NLRP3信号通路的调控机制研究

[目的]研究清热祛浊胶囊(QRQZ)对非酒精性脂肪肝炎(NASH)模型小鼠的治疗效果及对核转录因子-κB(NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路的影响。[方法]通过蛋氨酸和胆碱缺乏(MCD)饮食诱导建立NASH小鼠模型,并灌胃不同剂量的QRQZ。通过检测各组小鼠体质量、肝指数、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC),肝苏木素-伊红(HE)染色及油红O染色评估QRQZ对NASH模型小鼠的治疗作用;通过检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)水平评估QRQZ对NASH模型小鼠氧化应激水平;通过酶联免疫吸附测定(ELISA)检测白细胞介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平评估QRQZ对NASH模型小鼠炎症的影响;通过检测磷酸化核因子κB抑制蛋白(p-IκB)、磷酸化核转录因子κB P65(p-NF-κB P65)、NLRP3、凋亡相关斑点样蛋白(ASC)、活化的半胱氨酸天冬氨酸蛋白酶1(cleaved Caspase-1)、mature IL-1β的蛋白水平以及NLRP3、ASC、Caspase-1、IL-1β的mRNA表达来评估QRQZ对NASH小鼠NF-κB/NLRP3信号通路的影响。[结果] QRQZ可改善MCD引起的体质量减轻,降低肝指数,降低血清ALT、AST活性及TC、TG水平,同时改善肝组织病理学变化,提示QRQZ对NASH模型小鼠具有治疗作用;此外,QRQZ提升肝组织中SOD、GSH-Px活性,降低了MDA水平,降低了IL-6、IL-1β、iuTNF-α炎症因子水平,提示了QRQZ的抗氧化及抗炎作用;进一步研究发现QRQZ降低了IκB与P65的磷酸化水平,减少NLRP3、ASC、Caspase-1、IL-1β蛋白及基因表达。提示QRQZ干预抑制了NASH小鼠NF-κB/NLRP3信号通路活化。[结论] QRQZ对NASH模型小鼠具有治疗作用,并且可以提升抗氧化能力改善炎症,其作用机制可能与抑制NF-κB/NLRP3信号通路活化有关。

Regulation of heme oxygenase expression by alcohol,hypoxia and oxidative stress

AIM:To study the effect of both acute and chronic alcohol exposure on heme oxygenases(HOs) in the brain,liver and duodenum.METHODS:Wild-type C57BL/6 mice,heterozygous Sod2 knockout mice,which exhibit attenuated manganese superoxide dismutase activity,and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia.For acute alcohol exposure,ethanol was administered in the drinking water for 1 wk.Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies.HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.RESULTS:Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice.It did not alter liver HO-1 expression,nor HO-2 expression in the brain,liver or duodenum.In contrast,acute alcohol exposure decreased both liver HO-1 and HO-2 expression,and HO-2 expression in the duodenum of wild-type mice.The decrease in liver HO-1 expression was abolished in ARNT+/-mice.Sod2+/-mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression.However,alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2+/-mice.Collectively,these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner.Chronic alcohol exposure alters brain and duodenal,but not liver HO expression.However,acute alcohol exposure inhibits liver HO-1 and HO-2,and also duodenal HO-2 expression.CONCLUSION:The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.

孟德尔随机化研究铁死亡在非酒精性脂肪肝病的发生机制及作用研究

目的 探讨孟德尔随机化研究铁死亡在非酒精性脂肪肝病的发生机制及作用。方法 基于铁死亡与非酒精性脂肪肝病的全基因组关联研究结果数据,采用IVW和MR-Egger两种两样本MR方法评估了包括:氧化应激、脂质过氧化、生长因子、趋化因子、炎性因子、肿瘤坏死因子及其他多个细胞因子与铁死亡和非酒精性脂肪肝病的因果关系,并采用多种方法完成其多效性检验。结果 确定氧化应激、脂质过氧化及炎性因子的效应值评估需要选择MR-Egger回归方法进行干预,其余参数均选择IVW为主要方法进行效应值统计。同时,入组的铁死亡相关的细胞因子对非酒精性脂肪肝的I2GX>0.9,使得该方法使用时不需要矫正偏差;铁死亡与NAFLD显著相关,铁死亡能通过脂质过氧化及炎症反应等,增加NAFLD的发生(IVW:OR=1.03,95%CI:1.01~1.04);趋化因子CXCL19与肝细胞因子对NAFLD的发生存在潜在效应;Q检验P与MR-Egger回归方法截距P>0.05,说明MR分析结果未见多效应性偏差。结论 从基因层面而言,铁死亡能直接参与非酒精性脂肪肝的发生和发展,并伴有脂质过氧化及炎性反应,造成肝脏细胞变性,亦可为临床治疗提供新的思路,但仍需要进一步研究来全面的评估其相关性。

八种食用菌提取物对不同类型肝细胞损伤保护作用

探究刺芹侧耳(Pleurotus eryngii)、瓦尼桑黄(Sanghuangporous vaninii)、灰树花(Grifola frondosa)、赤芝(Ganoderma lucidum)、香菇(Lentinula edodes)、蟹味菇[Hypsizygus marmoreus(brown cultivar)]、白玉菇[H.marmoreus(white cultivar)]的子实体和樟芝(Antrodia cinnamomea)菌丝体水提物及醇提物对乙醇、H_(2)O_(2)和对乙酰氨基酚诱导肝细胞损伤的保护作用。研究结果表明:在乙醇诱导的肝损伤中,相较于乙醇组,质量浓度为25、50、100μg·mL^(-1)的灰树花和樟芝醇提物和质量浓度为25、100、400μg·mL^(-1)的蟹味菇、刺芹侧耳、灰树花、香菇、白玉菇水提物均可显著提高肝细胞存活率。在H_(2)O_(2)诱导的肝损伤中,相较于H_(2)O_(2)组,质量浓度为25、50、100μg·mL^(-1)的瓦尼桑黄和樟芝醇提物和质量浓度为25、100、400μg·mL^(-1)的刺芹侧耳、灰树花、香菇水提物均可显著提高肝细胞存活率。在对乙酰氨基酚诱导的肝损伤中,相较于乙酰氨基酚组,仅质量浓度为50、100μg·mL^(-1)的瓦尼桑黄醇提物极显著提高肝细胞存活率。相关性分析表明:多酚、黄酮含量与对乙酰氨基酚诱导的肝损伤的保护作用呈显著正相关,多糖含量与H_(2)O_(2)诱导的肝损伤的保护作用呈显著正相关。综上,八种食药用菌提取物在三种肝损伤中均表现出一定的保肝功效,其保肝活性的发挥与其多酚、黄酮含量密切相关。研究结果可为筛选具有保肝功效的食用菌资源及保肝功能产品的开发提供参考。

马里苷对酒精性脂肪肝的保护作用及机制

目的探究马里苷对酒精性脂肪肝(AFL)的保护作用及可能机制。方法以高度白酒灌胃建立小鼠AFL模型,将小鼠按体重随机分为正常对照组(n=9,0.5%羧甲基纤维素钠溶液)、模型组(n=10,0.5%羧甲基纤维素钠溶液)和马里苷75、150 mg/kg组(n=9);每天灌胃给药1次,连续30 d。末次给药后,测定小鼠肝组织中甘油三酯(TG)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平,观察其肝组织病理形态学变化,测定其肝组织中过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶1(CPT-1)和二脂酰甘油酰基转移酶(DGAT)蛋白表达水平。以乙醇诱导结合硫酸亚铁和油酸建立大鼠BRL肝细胞损伤模型,以3、6、12μmol/L马里苷干预24 h,观察肝细胞的脂滴分布,测定细胞中TG、MDA、SOD水平及PPARα、CPT-1、DGAT蛋白表达;经MK886(PPARα抑制剂,10μmol/L)预处理后,将造模肝细胞给予12μmol/L马里苷干预24 h,测定细胞中上述蛋白表达。结果动物实验中,与模型组比较,马里苷75、150 mg/kg组小鼠肝脏脂肪变性程度显著减轻,TG、MDA水平和DGAT蛋白表达水平显著降低(P<0.05或P<0.01),SOD水平及PPARα、CPT-1蛋白水平表达水平显著升高(P<0.05或P<0.01)。细胞实验中,3、6、12μmol/L马里苷作用后可显著减少乙醇诱导肝细胞中脂质堆积,降低细胞中TG、MDA水平和DGAT蛋白表达水平(P<0.05或P<0.01),升高细胞中SOD水平及PPARα、CPT-1蛋白表达水平(P<0.05或P<0.01),且在MK886预处理后马里苷对PPARα、CPT-1和DGAT蛋白表达的影响消失。结论马里苷对AFL具有保护作用,其作用机制可能与抑制氧化应激损伤、改善PPARα介导的脂质代谢信号通路有关。

健脾理气化湿方对非酒精性脂肪性肝炎小鼠肝细胞损伤、氧化应激和硝化应激的影响

目的观察健脾理气化湿方对非酒精性脂肪性肝炎(NASH)小鼠肝细胞损伤、氧化应激和硝化应激的影响,探讨其治疗NASH的作用机制。方法32只雄性C57BL/6J小鼠随机分为对照组、模型组和中药低、高剂量组,每组8只。对照组予普通饲料喂养,其余各组予高脂饲料喂养,连续16周。第13周开始,对照组和模型组予0.4%羧甲基纤维素钠溶液灌胃,中药低、高剂量组分别予相应剂量药物灌胃。生化仪检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)含量,HE染色、油红O染色观察肝脏组织病理变化,试剂盒检测肝组织三酰甘油(TG)含量和髓过氧化物酶(MPO)活性,免疫荧光染色检测肝组织CD11b阳性表达,RT-PCR检测肝组织NADPH氧化酶1(NOX1)、中性粒细胞胞浆因子1(NCF1)mRNA表达,Western blot检测肝组织诱导型一氧化氮合酶(iNOS)、3-硝基酪氨酸(3-NT)蛋白表达。结果与对照组比较,模型组小鼠肝细胞弥漫性脂肪变性,肝细胞肿胀、有明显炎性细胞浸润,油红O染色见大量脂滴形成;血清ALT、AST含量显著升高(P<0.05),肝组织TG含量、MPO活性显著升高(P<0.05),CD11b阳性表达升高,肝组织NOX1、NCF1 mRNA表达显著升高(P<0.05),iNOS、3-NT蛋白表达显著升高(P<0.05)。与模型组比较,中药低、高剂量组小鼠肝脏脂肪变性、炎性细胞浸润减轻,脂滴明显减少;血清ALT、AST含量显著降低(P<0.05),肝组织TG含量、MPO活性显著降低(P<0.05),CD11b阳性表达降低,肝组织NOX1、NCF1 mRNA表达显著降低(P<0.05),3-NT蛋白表达显著降低(P<0.05),中药高剂量组小鼠肝组织i NOS蛋白表达显著降低(P<0.05)。结论健脾理气化湿方可能通过减轻肝脏氧化应激和硝化应激,减轻NASH小鼠肝细胞损伤、脂质沉积和炎症反应,发挥治疗NASH作用。

副干酪乳杆菌FZU103对小鼠酒精性肝损伤的防控作用

目的:探究副干酪乳杆菌FZU103(Lactobacillus paracasei FZU103,LP-FZU103)对酒精性肝损伤(alcoholic liver injury,ALI)的防控作用。方法:选取36只SPF级ICR小鼠,随机分为空白组、模型组、实验组(LP-FZU103干预),实验6周后测定体质量及脏器系数、血清及肝脏生化、肝组织病理学及炎症因子、肝功能相关基因转录和肠道菌群组成。结果:与模型组相比,LP-FZU103干预可改善ALI小鼠的脏器系数和肝组织病理损伤程度,显著降低血清中总胆固醇、甘油三酯和低密度脂蛋白胆固醇浓度以及谷丙转氨酶和谷草转氨酶活性,提高血清高密度脂蛋白胆固醇浓度;显著提高肝脏中过氧化氢酶和超氧化物歧化酶活性以及谷胱甘肽含量,降低肝脏中丙二醛含量和白细胞介素6、干扰素γ水平;显著上调脂质代谢相关基因Ldlr及下调Acc1、Hmgcr和Cd36的mRNA水平;显著增加小鼠肠道中约氏乳杆菌(Lactobacillus johnsonii)、罗伊氏乳杆菌(Lactobacillus reuteri)、副干酪乳杆菌(Lactobacillus paracasei)等有益细菌的相对丰度。结论:LP-FZU103干预可一定程度防控小鼠ALI的发生,这与其改善肠道菌群及肝脏代谢功能密切相关。

Advanced Progress on Adaptive Stress Response of Oenococcus oeni

Oenoccoccus oeni is an alcohol-tolerant, acidophilic lactic acid bacterium with its ability to perform malolactic fermentation in wine, which is of fundamental importance in oenology. As a representative of the wine bacterium with remarkable adaptability to the very harsh physicochemical conditions of wine, many studies were carded out for its applied interest and focused mainly on its stress response mechanisms of O. oeni. on both physiological and molecular levels. In this review, three main stress response mechanisms in O. oeni during culturing process were addressed. Of them, various solute transporters and secondary metabolic energy-generating systems were utilized to control the intracellular environment and the energetic status of O. oeni. The changes in cell membrane fatty acid composition profiles and synthesis of stress proteins, especially small heat shock proteins were required for active cell response to maintain membrane integrity and function under stress conditions. The study on stress response of O. oeni played an important role on culture bacteria selection, making inoculation culture and construction of other engineering bacteria.

陈皮酵素对小鼠酒精性肝损伤及肠道菌群的调节作用

目的探讨陈皮酵素(Pericarpium citri reticulatae fermentation liquor,PF)对小鼠酒精性肝损伤和肠道的调节作用。方法将40只C57BL/6雄性小鼠随机分为正常组、模型组、阳性药物组[100mg/(kg·d)水飞蓟宾(silibinin,Sly)]和陈皮酵素组[500 mg/(kg·d)PF],每组10只,持续给药干预2周。通过分子生物学检测生物化学和病理学指标;16S rDNA高通量测序技术检测分析粪便微生物群。结果组织切片结果显示陈皮酵素可以显著改善酒精性肝损伤小鼠的肝脏和回肠组织损伤,减少酒精诱导的肝脏脂质积累。此外,陈皮酵素显著降低肝脏组织促炎因子[白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]的水平,缓解酒精引起的氧化应激。同时,陈皮酵素可修复酒精引起的肠道菌群紊乱,维持肠道菌群数量,修复肠道黏膜屏障损伤。结论陈皮酵素可改善酒精性肝损伤,其机制与抗氧化、抗炎和调节肠道菌群紊乱有关,值得推广应用与开发。

司美格鲁肽治疗2型糖尿病合并非酒精性脂肪性肝病的临床疗效及对氧化应激和炎症因子的影响

目的探讨司美格鲁肽治疗2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)的疗效及对氧化应激和炎症因子的影响。方法选择2021年7月至2022年12月新乡医学院第一附属医院内分泌科收治的80例T2DM合并NAFLD患者为研究对象,根据随机数字法将患者分为观察组和对照组,每组40例。对照组患者给予吡格列酮二甲双胍、达格列净治疗,观察组患者给予吡格列酮二甲双胍、达格列净和司美格鲁肽治疗。比较2组患者治疗前、治疗24周后的糖化血红蛋白(HbA1c)、空腹血糖(FBG)、餐后2 h血糖(2hPG)、体质量、体质量指数(BMI)、腰围、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转移酶(GGT)、控制衰减指数(CAP)、肝硬度值(LSM)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、脂质过氧化物(LPO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平的变化。结果治疗24周后,观察组与对照组总有效率分别为92.5%(37/40)、72.5%(29/40),观察组患者的总有效率显著高于对照组(χ^(2)=5.541,P<0.05)。治疗前,2组患者的体质量、BMI、腰围、HbA1c、FBG、2hPG、ALT、AST、GGT、CAP、LSM、MDA、GSH-PX、LPO、TNF-α、IL-6、IL-10水平比较差异无统计学意义(P>0.05);2组患者治疗24周后的体质量、BMI、腰围、HbA1c、FBG、2hPG、ALT、AST、GGT、CAP、LSM、MDA、LPO、TNF-α、IL-6、IL-10水平均显著低于治疗前,GSH-PX显著高于治疗前(P<0.05);治疗24周后,观察组患者的体质量、BMI、腰围、HbA1c、FBG、2hPG、ALT、AST、GGT、CAP、LSM、MDA、LPO、TNF-α、IL-6、IL-10水平均显著低于对照组,GSH-PX显著高于对照组(P<0.05)。治疗期间,观察组与对照组不良反应发生率分别为17.5%(7/40)、12.5%(5/40),2组不良反应发生率的比较差异无统计学意义(P>0.05)。结论司美格鲁肽能够显著降低T2DM合并NAFLD患者的FBG、2hPG及HbA1c水平,减轻患者体质量并缩小腰围,降低肝酶水平,改善肝脏脂肪含量及肝纤维化程度,减轻机体氧化应激并降低机体炎症指标。

认知行为干预结合健康教育对急性酒精中毒患者心理应激的影响

目的探讨认知行为干预结合健康教育对急性酒精中毒患者心理应激的影响。方法选取2023年1~3月扬州大学附属医院西区分院急诊科收治的急性酒精中毒患者64例为研究对象,根据入院顺序进行分组,将2023年1月1~31日收治的32例急性酒精中毒患者作为对照组,将2023年3月1~31日收治的32例急性酒精中毒患者作为试验组。对照组实施急诊输液室常规干预,试验组在对照组基础上实施认知行为干预结合健康教育,对比2组间自我效能(GSES)评分、焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分、疾病不确定感量表(MUIS-A)以及随访1个月时、2个月时与3个月时的饮酒次数。结果试验组患者干预后的SAS、SDS评分较对照组均明显降低(P<0.05)。干预后,2组患者自我效能(GSES)评分较干预前明显升高,但试验组更高(P<0.05)。2组患者干预后疾病不确定感(MUIS-A)评分均降低,且试验组降低更明显(P<0.05)。与对照组比较,试验组患者随访1个月、2个月与3个月时的饮酒次数明显减少(P<0.05)。结论对急性酒精中毒患者实施认知行为干预结合健康教育,可明显降低患者心理应激反应,提高患者自我效能感,减轻患者疾病不确定感,减少患者饮酒次数,对改善患者心理状态有正向影响,建议应用与推广。

未折叠蛋白反应在非酒精性脂肪性肝病中的作用研究进展

内质网应激(endoplasmic reticulum stress,ERS)下的未折叠蛋白反应(unfolded protein response,UPR)可调节脂质代谢,与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的进展有极大的相关性。当肝细胞在受到某些刺激,如缺氧或氧化应激时,会发生ERS,启动UPR以恢复细胞稳态。ERS又有急性ERS和慢性持续性ERS两种形式,急性ERS所触发的UPR是维持细胞稳态的重要反应机制,而慢性持续性ERS会启动细胞的凋亡程序,诱导细胞凋亡,与NAFLD的发生发展密切相关,其可能是NAFLD进程中的关键因素。本文回顾了NAFLD进展与UPR的联系,从脂质代谢、自噬角度讨论了UPR与NAFLD的关系,以期进一步深入了解NAFLD的发病机制,为NAFLD的预防和治疗提供指导。

氧化应激与酒精依赖认知损害的关系

酒精是中枢神经系统的抑制剂,长期大量饮酒会形成酒精依赖。酒精依赖是一种复杂而严重精神疾病,可导致日常身体、心理和社会功能的紊乱。目前,酒精依赖患病率约为2.6%,临床缺乏有效的预防策略、治疗措施和康复方案是导致酒精依赖全球健康负担不断增加的主要因素。长期反复饮酒和戒断可引起大脑结构和功能改变,造成神经心理认知功能损害,严重者可导致痴呆,严重危害人类的身心健康。酒精依赖造成的认知损害病因复杂,其中氧化应激在酒精依赖认知功能损害中起着关键作用。本综述针对酒精依赖所致认知损害与氧化应激的关系进行文献综述,以期为酒精依赖所致认知功能障碍的诊断和治疗提供一定借鉴。