中药对酒精性肝损伤的保护作用

长期大量饮酒导致的酒精性肝病是一类常见的危害人类健康的疾病,目前尚无确切的治疗方法。近年来,中草药在预防和治疗酒精性肝病方面的潜在疗效引起了人们的广泛关注。本文就近年来中草药在预防和治疗酒精性肝损伤方面的研究做一综述。     

杜仲总黄酮对小鼠急性肝损伤的保护作用

研究了杜仲总黄酮对四氯化碳(CCl_4)诱导的急性肝损伤的保护作用。通过腹腔注射CCl_4诱导小鼠急性肝损伤,检测小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)的含量、肝脏中超氧化物歧化酶(SOD)的活性、谷胱甘肽(GSH)和丙二醛(MDA)的含量,考察杜仲总黄酮的保肝作用。结果表明:杜仲总黄酮能显著降低急性肝损伤小鼠血清中的ALT、AST活性与肝脏中的MDA含量,并能提高肝脏中的SOD与GSH活性。杜仲总黄酮对CCl_4引起的急性肝损伤小鼠具有保护作用,其作用机制可能与抗氧化作用有关。     

杞枣养肝颗粒对大鼠酒精性肝损伤模型的影响

研究杞枣养肝颗粒对大鼠酒精性肝损伤模型的影响。采用56°二锅头灌胃法建立大鼠酒精性肝损伤模型,将大鼠随机分为6组,分别灌服杞枣养肝颗粒混悬液、护肝宁片混悬液和相同体积的生理盐水,连续给药5 d,于第5 d后开始测定。检测各组大鼠血清中AST、ALT以及大鼠肝匀浆中的MDA、SOD的含量,显微镜下观察各给药组大鼠肝组织切片病理组织学变化。实验结果显示：与模型组对照,杞枣养肝颗粒中剂量组、低剂量组和护肝宁片对照组血清中AST、ALT水平及肝匀浆中MDA水平显著下降（P<0.01）,肝匀浆中SOD水平明显升高（P<0.01）。各给药组肝组织病理切片显示：阳性对照组、杞枣养肝颗粒低剂量组和中剂量组能显著对抗56°二锅头。杞枣养肝颗粒能明显降低大鼠酒精性肝损伤血清中AST、ALT水平及肝匀浆中MDA水平,升高肝匀浆中SOD水平,各组间差异具有显著的统计学意义,结合病理切片说明此中成药能改善肝损伤细胞的结构、形态、炎细胞浸润程度从而起到保护肝脏的作用。     

丙型病毒性肝炎合并非酒精性脂肪性肝病的研究进展

丙型病毒性肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)引起的一种全球分布的传染性疾病,大部分患者可发展为慢性丙型肝炎(chronic hepatitis C,CHC)、肝硬化、肝癌。非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一类排除酒精及明确因素损伤,与肥胖、胰岛素抵抗等有关的综合性慢性肝脏病变。HCV合并NAFLD可加速肝脏疾病的发生和发展,更易发展为慢性肝炎、肝硬化和肝细胞肝癌。本文主要从CHC合并NAFLD的流行病学现状、两种疾病之间的相互影响、作用机制、诊断及治疗等方面作一综述。     

激活素A及激活素结合蛋白在急性酒精性肝损伤小鼠肝组织中的表达

目的探讨激活素A(Activin A)及激活素结合蛋白(Follistatin,FS)在急性酒精性肝损伤小鼠肝组织中的表达。方法通过1次/12 h给予小鼠5 g/Kg酒精连续灌胃3次,复制急性酒精性肝损伤小鼠模型,采用实时定量RT-PCR检测小鼠肝组织Activin A及FS mRNA表达水平,免疫组织化学染色观察小鼠肝组织Activin A及FS蛋白的表达水平。结果急性酒精性肝损伤小鼠肝组织Activin A mRNA和蛋白表达水平均显著高于对照组(P<0.01);FS mRNA和蛋白表达水平与对照组比较,差异均无统计学意义(P>0.05)。结论急性酒精性肝损伤小鼠肝组织Activin A-FS表达失衡,以Activin A升高为主,提示Activin A-FS系统失衡可能与酒精性肝损伤有关。     

紫花前胡素对CCl_4致小鼠肝损伤的保护作用

目的:观察紫花前胡素(Decursin)对四氯化碳(CCl_4)致小鼠急性肝损伤的改善作用并探讨其可能的机制。方法:50只健康雄性ICR小鼠随机分成5组,正常对照组,急性肝损伤模型组,紫花前胡素低、中、高剂量组。隔天灌胃给药,共30天;腹腔注射CCl_4玉米油溶液诱导小鼠急性肝损伤,处死取血和肝脏。测定各组小鼠血清中丙氨酸氨基转移酶(ALT)及天门冬氨酸氨基转移酶(AST)的活性,小鼠肝脏组织中CYP2E1的含量,在体外检测紫花前胡素清除超氧阴离子及羟自由基的能力。结果:不同剂量紫花前胡素能够抑制CCl_4引起的血清ALT及AST的升高,并且能够减少肝组织匀浆中CYP2E1的产生。此外,紫花前胡素在体外能够清除超氧阴离子及羟自由基。结论:紫花前胡素对CCl_4导致的小鼠急性肝损伤具有一定的保护作用,推测可能是通过抑制细胞色素酶CYP2E1的产生进而减少三氯甲基等自由基的产生以及自身的抗氧化能力实现预防和改善急性肝损伤。     

酒精性肝病的病理机制研究进展

酒精性肝病(ALD)是全球肝脏相关死亡的主要原因,其发病率在全球逐年增高,在中国已成为继病毒感染之后的第二大肝损伤原因.ALD可表现为一系列的病理变化,包括脂肪变性,肝炎、肝纤维化和硬化,甚至导致肝癌的发生.由于其病理机制复杂,目前尚无有效的临床治疗手段和药物.深入探讨ALD的病理机制,具有重要的科学研究意义和临床应用...     

122例酒精性肝病患者的临床研究

目的探讨酒精性肝病患者的治疗方法与临床疗效。方法回顾性分析我院收治的122例酒精性肝病患者的临床资料,所有患者随机分为2组,实验组61例患者在常规治疗的基础上采用阿托莫兰联合易善复进行治疗,对照组61例患者采用常规治疗的方法进行治疗。治疗结束后观察2组的临床疗效。结果实验组的疗效明显高于对照组,2组差异有统计学意义(P<0.05)。结论阿托莫兰联合易善复治疗酒精性肝病疗效肯定,能明显改善酒精性肝病患者的临床症状,并促进黄疸的消退,促进肝功能恢复。     

木犀草素与奥贝胆酸联合用药对非酒精性脂肪肝模型小鼠的干预作用

目的:探讨木犀草素与奥贝胆酸联合用药对非酒精性脂肪性肝(NAFLD)模型小鼠的治疗作用。方法:将50只C57BL/6小鼠分为空白组、模型组、木犀草素组、奥贝胆酸组、木犀草素与奥贝胆酸联用组,每组10只,除空白组外,其余均用CCl_4和高脂饲料诱导NAFLD模型,对木犀草素组小鼠灌胃木犀草素(30 mg/kg),奥贝胆酸组灌胃奥贝胆酸(30 mg/kg)以及两者联合给药组灌胃[木犀草素(30 mg/kg)+奥贝胆酸(30mg/kg)],每天给药1次,连续4周。4周末,称量各组小鼠体重,断颈处死后剖取肝脏称重,计算肝指数。HE染色观察肝脏组织病理情况。结果:与空白组相比,模型组肝指数显著升高(P0.01),肝小叶结构存在损伤。与模型组相比,木犀草素与奥贝胆酸联用组肝指数降低(P0.01),肝组织损伤现象较改善。结论:木犀草素和奥贝胆酸联用可改善NAFLD模型小鼠肝损伤,具有一定的治疗作用。     

Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.     

复肝肽口服液对大鼠四氯化碳慢性肝损伤的保护作用

目的观察复肝肽口服液(主要成分为新生牛肝活性肽)对大鼠四氯化碳(CCl4)慢性肝损伤的保护作用。方法制备大鼠CCl4慢性肝损伤模型,观察复肝肽口服液对慢性肝损伤大鼠红、白细胞数、血色素、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)、白球蛋白比例(A/G)的影响。结果与模型对照组比较,复肝肽3个剂量组大鼠的A/G值均明显升高,肝组织病变明显减轻,高剂量组ALT、AST明显降低。结论复肝肽口服液对慢性肝损伤有明显的保护作用。     

Hepatoprotective Effect of Oyster Peptide on Alcohol-Induced Liver Disease in Mice

Alcohol-induced liver disease (ALD) has become one of the major global health problems, and the aim of this study was to investigate the characterization of the structure as well as the hepatoprotective effect and mechanism of oyster peptide (OP, MW < 3500 Da) on ALD in a mouse model. The results demonstrate that ethanol administration could increase the activities of aspartate aminotransferase (AST), alanine transaminase (ALT), γ-Glutamyl transferase (GGT), reactive oxygen species (ROS), malondialdehyde (MDA), and triglycerides (TG), as well as increase the interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) levels (p < 0.01), and reduce the activity of superoxide dismutase (SOD) and the concentration of glutathione (GSH). Those changes were significantly reversed by the application of different doses of OP. Furthermore, the mRNA expressions of nuclear factor elythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and quinone oxidoreductase1 (NQO1) were significantly up-regulated in OP groups, and the mRNA expressions of nuclear factor kappa-light chain enhancer of B cells (NF-κB), TNF-α, and IL-6 were markedly reduced in OP groups compared to that of the model group. Thus, OP had a significant protective effect on ALD through the enhancement of the in vivo antioxidant ability and the inhibition of the inflammatory response as possible mechanisms of action, which therefore suggests that OP might be useful as a natural source to protect the liver from alcohol damage.     

Correlations of Hepatic Hemodynamics,Liver Function,and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.     

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.     

Long-Term Adverse Effect of Liver Stiffness on Glycaemic Control in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease: A Pilot Study

Currently, there are limited data regarding the long-term effect of liver stiffness on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). We prospectively followed an outpatient sample of 61 consecutive postmenopausal women with T2DM and NAFLD who had baseline data on liver ultrasonography and Fibroscan^®-assessed liver stiffness measurement (LSM) in 2017 and who underwent follow-up in 2022. Haemoglobin A1c (HbA1c) was measured both at baseline and follow-up. At baseline, 52 patients had NAFLD (hepatic steatosis) alone, and 9 had NAFLD with coexisting clinically significant fibrosis (defined as LSM ≥ 7 kPa on Fibroscan^®). At follow-up, 16 patients had a worsening of glycaemic control (arbitrarily defined as HbA1c increase ≥ 0.5% from baseline). The prevalence of NAFLD and coexisting clinically significant fibrosis at baseline was at least three times greater among patients who developed worse glycaemic control at follow-up, compared with those who did not (31.3% vs. 8.9%; p = 0.030). In logistic regression analysis, the presence of NAFLD and clinically significant fibrosis was associated with an approximately 4.5-fold increased likelihood of developing worse glycaemic control at follow-up (odds ratio 4.66, 95% confidence interval 1.07–20.3; p = 0.041), even after adjustment for baseline confounding factors, such as age, body mass index, haemoglobin A1c (or HOMA-estimated insulin resistance) and use of some glucose-lowering agents that may positively affect NAFLD and liver fibrosis. In conclusion, our results suggest that the presence of Fibroscan^®-assessed significant fibrosis was associated with a higher risk of developing worse glycaemic control in postmenopausal women with T2DM and NAFLD.     

Protective Effects of Voluntary Exercise on Hepatic Fat Accumulation Induced by Dietary Restriction in Zucker Fatty Rats

Weight control based on dietary restriction (DR) alone can cause lipid metabolic failure and progression to fatty liver. This study aimed to investigate the effect of exercise on preventing DR-induced hepatic fat accumulation in Zucker fatty (ZF) rats by focusing on the relationship between adipose tissue lipolysis and hepatic fat uptake. Six-week-old male ZF rats were randomly assigned to obese, DR, or DR with exercise (DR + Ex) groups. The DR and DR + Ex groups were fed a restricted diet, with the latter also undergoing voluntary exercise. After 6 weeks, hepatic fat accumulation was observed in the DR group, whereas intrahepatic fat was markedly reduced in the DR + Ex group. Compared with the obese (Ob) group, the DR group exhibited 2.09-fold expression of hepatic fatty acid translocase (FAT)/CD36 proteins (p < 0.01) and 0.14-fold expression of hepatic fatty acid-binding protein (FABP)1 (p < 0.01). There were no significant differences between the DR + Ex group and the Ob group. FAT/CD36 and hepatic triglyceride (TG) expression levels were strongly positively correlated (r = 0.81, p < 0.001), whereas there was a strong negative correlation between FABP1 and hepatic TG expression levels (r = −0.65, p < 0.001). Our results suggest that hepatic fat accumulation induced by DR in ZF rats might be prevented through exercise-induced modifications in FAT/CD36 and FABP1 expression.     

Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests

The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. “Dynamic” liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope ¹³C. Hepatocellular metabolization of the substrate will generate ¹³CO₂, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of ¹³CO₂ are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. ¹³C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, ¹³C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. ¹³C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of ¹³C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.