黄连素联合二甲双胍治疗2型糖尿病合并非酒精性脂肪肝的临床观察

目的 观察黄连素联合二甲双胍治疗2型糖尿病合并非酒精性脂肪肝的疗效及安全性.方法 选择初诊2型糖尿病合并非酒精性脂肪患者78例,治疗组(黄连素+二甲双胍)38例和对照组(二甲双胍)40例.治疗前后测定体重指数(BMI)、FPG、2hPG、HbA1c、FINS,血脂(TC、TG、HDL-C、LDL-C),肝功能(AST、ALT、GGT),计算胰岛素抵抗指数(HOMA-IR).观察期16周.结果 与对照组相比,治疗组可进一步降低血糖、减轻体重、增加胰岛素敏感性(P＜ 0.05);治疗组的血脂、肝功能的改善明显优于对照组(P＜0.01).结论 黄连素联合二甲双胍治疗2型糖尿病合并NAFLD具有一定的疗效.     

瘦素改善2型糖尿病ob/ob小鼠糖和脂质代谢作用机制的探讨

目的 研究瘦素对2型糖尿病小鼠糖脂代谢及肝功能的改善作用,并从氧化应激、内质网应激和胰岛素抵抗等方面探讨其可能机制。方法 选用瘦素缺陷的ob/ob小鼠作为2型糖尿病模型,根据是否给予瘦素处理分为两组（1 mg/（kg·d）, 腹腔内注射）;选用野生型C57BL/6J小鼠为正常对照。测定血清甘油三酯（triglyceride,TG）和总胆固醇（total cholesterol,TC）反映脂质代谢状况,血清谷丙转氨酶（alanine transaminase,ALT）和谷草转氨酶（aspartate aminotransferase,AST）反映肝功能; 酶联免疫吸附实验测定胰岛素水平;Western blot检测氧化应激指标还原烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（nicotinamide adenine dinucleotide phosphate reduced oxidase 4,NOX4）和过氧化氢酶 （catalase,CAT）、内质网应激标志葡萄糖调节蛋白78（glucose-regulated protein 78,GRP78）水平,胰岛素调控糖脂代谢通路蛋白激酶B（protein kinase B,AKT）的激活。结果 与野生型小鼠比较,ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆升高（均有P<0.05）;与ob/ob小鼠比较,经瘦素处理的ob/ob小鼠血糖、TG和TC、ALT和AST活力以及胰岛素水平皆下降（均有P<0.05）。与野生型小鼠比较,ob/ob小鼠肝脏NOX4和GRP78水平增高（均有P<0.05）,CAT和p-AKT水平降低（均有P<0.05）;与未经瘦素处理的ob/ob小鼠相比,经瘦素处理的ob/ob小鼠肝脏中NOX4、GRP78降低（均有P<0.05）,CAT和p-AKT升高（均有P<0.05）。结论 瘦素可改善2型糖尿病小鼠糖脂代谢和肝功能,作用机制可能与其减轻肝脏氧化应激和内质网应激以及恢复对胰岛素的敏感性有关。     

Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice

The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20-22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20-22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet-induced fatty liver disease in mice. Wild-type (WT) and Ldlr(-/-) C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF-high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1α1), and oxidative stress (heme oxygenase-1) (P ≤ 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr(-/-) mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr(-/-) mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice.     

Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.     

Cinnamon may have therapeutic benefits on lipid profile,liver enzymes,insulin resistance,and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating insulin resistance and oxidative stress. In this study, we investigated the hypothesis that supplementation with cinnamon exerts an insulin sensitizer effect in patients with NAFLD. In a double-blind, placebo-controlled trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of cinnamon (each capsule contain 750 mg cinnamon) or 2 placebo capsules, daily for 12 weeks. During the intervention, all patients were given advice on how to implement a balanced diet and physical activity into their daily lives. In the treatment group (P < .05), significant decreases in HOMA (Homeostatic Model Assessment) index, FBS (fasting blood glucose), total cholesterol, triglyceride, ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma glutamine transpeptidase), and high-sensitivity C-reactive protein were seen, but there was no significant change in serum high-density lipoproteins levels (P = .122). In both groups, low-density lipoproteins decreased significantly (P < .05). In conclusion, the study suggests that taking 1500 mg cinnamon daily may be effective in improving NAFLD characteristics.     

学龄期儿童肥胖相关性脂肪肝及血脂代谢异常对照研究

目的 探讨兰州市学龄期儿童肥胖非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)、血脂代谢异常及其相关因素。方法 2011年6-10月选取3所小学1至6年级7~14岁小学生作为研究对象。选取年龄、性别匹配体质指数(body mass index, BMI)正常儿童作为对照。行腹部B超、采空腹静脉血5 mL进行实验室检查, 包括天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、谷氨酰转肽酶(gamma glutamyl transpeptidase, GGT)、总胆固醇(total cholesterol, CHOL)、甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)。结果 筛查出肥胖儿童80例, 与51例正常对照儿童比较, 肥胖组儿童的AST、ALT、GGT、CHOL、TG、LDL-C增高, HDL-C减低, 差异有统计学意义(P<0.05)。AST、ALT、GGT、TG、LDL-C与NAFLD发病呈正相关且为危险因素;HDL-C呈负相关为保护因素。肥胖儿童NAFLD检出率为27.5%(22/80);对照组未检出NAFLD, 肥胖儿童的NAFLD发生率明显高于正常儿童(P<0.05)。肥胖伴有NAFLD组较肥胖不伴NAFLD组AST、ALT、GGT、TG升高, HDL-C降低;差异具有统计学意义(P<0.05)。结论 肥胖导致学龄期儿童的肝功能损害、血脂代谢异常甚至可造成非酒精性脂肪肝的发生;非酒精性脂肪肝更进一步加重了肝功能损害及血脂代谢紊乱。     

脂肪肝患者A-FABP与胰岛素抵抗关系

目的探讨非酒精性脂肪肝病(NAFLD)患者血清脂肪细胞型脂肪酸结合蛋白(A-FABP)与胰岛素抵抗(IR)的关系。方法选择NAFLD患者119例,正常对照120人,测量身高、体重、腰围、臀围、体质指数及腰臀比,检测血清中总胆固醇、甘油三酯、高密度脂蛋白胆固醇、空腹血糖、空腹胰岛素抵抗指数及脂肪细胞型脂肪酸结合蛋白,并进行对比分析。结果NAFLD组血清A-FABP水平(13.45±5.06),明显高于对照组(9.14±5.00)μg/L(P0.01);且血清A-FABP水平与体质指数(BMI)、腰围(WC)、腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、空腹胰岛素(FINS)、空腹血糖(FPG)及胰岛素抵抗指数(HOMA-IR)呈正相关(r依次分别为0.560,0.538,0.384,0.426,0.341,0.302,0.345,0.256,0.359,P均0.01),而与HDL-C呈负相关(r=-0.337,P0.001)。结论NAFLD患者存在胰岛素抵抗,且血清A-FABP水平与胰岛素抵抗密切相关。     

非酒精性脂肪肝的基因研究

非酒精性脂肪肝（NAFLD）的发病率及脂肪性肝炎（NASH）的发生率与种族、民族和家族密切相关。脂肪性肝病是一组遗传-环境-代谢应激相关性的疾病,近年来NAFLD与遗传和基因的关系越来越受到人们的重视,研究NAFLD的基因应从肥胖、脂肪酸代谢、胰岛素抵抗等与NAFLD有关的环节的相关基因着手。     

二甲双胍治疗非酒精性脂肪性肝病68例体会

目的：探讨胰岛素增敏剂二甲双胍（MF）治疗非酒精性脂肪性肝病（NAFLD）的临床疗效。方法：回顾性分析某医院收治的68例NAFLD患者,采用MF1.5g/d口服治疗6个月,治疗后患者的临床症状和谷丙转氨酶（ALT）的改变情况。结果：MF可以明显降低ALT,改善NAFLD患者的临床症状。结论：二甲双胍用于治疗非酒精性脂肪性肝病,可以取得一定的临床疗效。     

Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets

OBJECTIVE: Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets. METHODS: C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver. RESULTS: The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity. CONCLUSIONS: Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets.     

非酒精性脂肪性肝病与动脉粥样硬化的关系

目的探讨非酒精性脂肪性肝病与动脉粥样硬化的关系及可能机制。方法122例门诊及住院患者根据B超检查结果分为2组,非酒精性脂肪性肝病组62例和正常对照组60例,对2组患者的动脉粥样硬化情况及其相关因素进行分析。结果非酒精性脂肪性肝病组BMI、腰臀比值、收缩压、舒张压、空腹血糖、胰岛素浓度、高密度脂蛋白、廿油三酯、高敏C反应蛋白、胰岛素抵抗指数及比例、谷丙转氨酶、谷草转氨酶和γ-氨酰转肽酶水平与对照组比较差异有统计学意义（P〈0．001）;总胆固醇、低密度脂蛋白、脂蛋白A两组水平相似;非酒精性脂肪性肝病组颈动脉斑块检出率和颈动脉内膜中层厚度均高于正常对照组,差异有统计学意义（P〈0．05）。经多变量分析发现,非酒精性脂肪性肝病和IMT及斑块呈显著相关（OR8．3,95％CI1．2～7．7,P=0．001）。结论非酒精性脂肪性肝病患者动脉粥样硬化的患病率高于正常对照组,非酒精性脂肪性肝病为动脉粥样硬化的危险因素,机制可能与内脏性肥胖、胰岛素抵抗和非酒精性脂肪性肝病状态下增加的氧化应激特性及血脂紊乱、炎症反应有关。     

Comparison of the Improvement Effect of Deep Ocean Water with Different Mineral Composition on the High Fat Diet-Induced Blood Lipid and Nonalcoholic Fatty Liver Disease in a Mouse Model

Accumulated lipid droplets in liver cause nonalcoholic fatty liver disease (NAFLD). Deep ocean water (DOW) containing high levels of magnesium, calcium, and potassium, etc. was proven to suppress hepatic lipid in obese rats fed high fat diet in the previous study. However, the effect of mineral compositions of DOW on the prevention of NAFLD is still unclear. This study removed calcium and potassium from DOW for modulating the mineral composition, and further compared the effects of DOW (D1(Mg + Ca + K)), DOW with low potassium (D2(Mg + Ca)), and DOW with low calcium and potassium (D3(Mg)) on the prevention of NAFLD in the mice model fed with high fat diet. In these results, DOW with high magnesium levels reduced serum and liver triglyceride and cholesterol levels and serum AST and ALT activities. However, when the calcium and/or potassium minerals were removed from DOW, the effects of reduction of triglyceride level, inhibition of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor-alpha (PPAR-α) expressions, and activation of superoxide dismutase, catalase, and glutathione reductase activities would be weaker. In conclusion, DOW including magnesium, calcium and potassium minerals has the strongest preventive effect on NAFLD in a mouse model by increasing the antioxidant system and inhibiting fatty acid biosynthesis.     

非酒精性脂肪性肝病FOXO1的表达及意义 FREE

目的 研究非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）患者分叉头框家族转录因子1（forkhead box containing protein O subfamily 1,FOXO1）表达的变化,以及转录因子和磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PEPCK)、葡萄糖 6 磷酸酶催化亚基(G6PC)之间的关系。同时探讨FOXO1在NAFLD发病机制中的作用。方法 对临床与病理确诊的NAFLD患者,用免疫组化法、逆转录聚合酶链反应（RT PCR）技术检测肝组织FOXO1的表达以及FOXO1、PEPCK和G6PC的mRNA水平。结果 非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）组、非酒精性单纯性脂肪肝（simple steatosis, SS）组的胰岛素抵抗指数（insulin resistance index, IR）显著高于健康对照组（P＜0.001);NASH组的血清丙氨酸转氨酶（ALT）显著高于SS组、对照组（P＜0.001或P＜0.05）,而SS组与对照组之差异无显著性(P＞0.05);3组的FOXO1阳性细胞数、FOXO1 mRNA、PEPCK mRNA、G6PC mRNA随病情的加重逐渐增加,组间差异有显著性（P＜0.001）。FOXO1 mRNA水平与IR、炎症评分和脂肪变性评分、PEPCK mRNA和G6PC mRNA表达正相关。结论 不能根据ALT正常与否决定是否肝穿刺活检。NASH患者的FOXO1表达和活性增强,FOXO1转录因子调节PEPCK和G6PC的表达,并与胰岛素抵抗有关。推测脂肪变性和炎性反应参与了FOXO1的调节。     

Lipoic Acid Exacerbates Oxidative Stress and Lipid Accumulation in the Liver of Wistar Rats Fed a Hypercaloric Choline-Deficient Diet

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.     

血清铁蛋自在非酒精性脂肪性肝病中的临床意义

目的探讨血清铁蛋白（sF）水平在成人非酒精性脂肪性肝病（NAFLD）患者中的临床意义。方法对入选的158例健康体检人群,进行血清铁蛋白、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）、空腹血糖（FBG）、血尿酸（UA）、谷草转氨酶（AST）及谷丙转氨酶（ALT）等各指标检测及肝脏超声检查,根据肝脏超声结果分为NAFLD组（68例）及正常对照组（90例）,比较两组间血清铁蛋白水平及血脂、血糖、尿酸、转氨酶等生化指标情况。结果NAFLD组中血清铁蛋白水平及甘油三酯、尿酸、转氨酶明显高于对照组,而高密度脂蛋白明显低于对照组（p〈0．01）;进一步相关性分析显示．血清铁蛋白与谷草转氨酶及谷丙转氨酶显著相关（r=0．260、0．299,P〈0．01）。结论血清铁蛋白水平的升高可能提示NAFLD患者肝损的一个有效指标,并在NAFLD的进展过程中可能起一定的作用。     

Obesity and Nonalcoholic Fatty Liver Disease

With the increasing prevalence of obesity and type 2 diabetes mellitus in the general population, nonalcoholic fatty liver disease (NAFLD) has become a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression. NAFLD affects one in three adults and one in 10 children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the anti-oxidant defenses in the liver deserve evaluation in carefully controlled trials.     

Effects of d-α-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-α and PPAR-γ. We investigated the effects of d-α-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-α and PPAR-γ in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-α-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-α-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-α expression and decreasing PPAR-γ expression. In conclusion, the oral administration of d-α-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-α and PPAR-γ in a high-fat diet-fed male mice.     

南宁市超重、肥胖儿童非酒精性脂肪肝患病情况分析

【目的】 了解南宁市超重、肥胖儿童非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)的检出情况。【方法】 对本院小儿内分泌科门诊就诊的180例超重、肥胖患儿进行身高、体重、腰围等测量,同时进行肝肾功能、血糖、胰岛素、肝脏B超等相关检测。【结果】 180例患儿中B超明确脂肪肝66例(男42例,女24例),非脂肪肝114例(男64例,女50例),NAFLD检出率为36.7%(66/180),其中男童检出率为39.6%(42/106),女童检出率为32.4%(24/74),男女差异无统计学意义(χ²=0.394,P=0.319);脂肪肝组体质指数、腰围、血压、血脂等指标均高于非脂肪肝组。【结论】 南宁市超重、肥胖儿童的NAFLD的发生率为36.7%,控制儿童超重、肥胖的发生,是防治儿童青少年NAFLD的重要措施;谷丙转氨酶能否用于超重、肥胖儿童NAFLD早期识别的依据值得探讨。     

安珐特联合易善复治疗非酒精性脂肪肝31例临床观察

目的 观察安珐特联合易善复治疗非酒精性脂肪性肝炎的临床疗效.方法 选取62例非酒精性脂肪性肝炎患者,随机分为两组.观察组31例,采用安珐特联合易善复治疗;对照组31例,采用易善复治疗.疗程均为3个月.观察两组临床症状、肝功能指标、血脂改善效果.结果 治疗组疗效总有效率明显优于对照组(P<0.01).治疗组临床症状、ALT、AST、甘油三酯、总胆固醇改善明显,与对照组比较,各指标差异均有统计学意义(P<0.05).结论 安珐特联合易善复对改善脂肪肝及肝功能有明显效果.