Role of Endotoxin and TNF in Developing NAFLD in Non-Obese Egyptian Patients

Background and aim of the work: Non-alcoholic fatty liver disease (NAFLD) was considered the hepatic presentation of insulin resistance and obesity for a long time. Studies on lean weighted Asian subjects with NAFLD revealed that NAFLD pathogenesis may be multifactorial. NAFLD is associated with disturbances in gut flora and excess expression of inflammatory mediators. This study aims to find out the relation of endotoxins absorbed from gut and the tumor necrosis factor alpha with NAFLD in non-obese Egyptian patient in comparison to obese patients and healthy control subjects. Patients and methods: This study was performed on three groups group I: Patients with NAFLD and body mass index 2. Group II: Patients with NAFLD and body mass index >25 kg/m2. Group III: healthy control subjects. Results: Group I had significantly higher endotoxin, tumor necrosis factor(TNF) alpha and ALT than group II (endotoxin 11.7 ± 1.7 ug/L vs 9.5 ± 1.4) (TNF 14.8 ± 5.3 vs 11.3 ± 3.3) (ALT 67.8 ± 5.3 IU/L vs 51.8 ± 4.2). There was a highly significant correlation between TNF, endotoxin levels and level of liver enzymes in group I and II. Conclusion: Endotoxemia and TNF alpha may contribute in the pathogenesis of NAFLD especially in non-obese patients.

Assessment of Urinary Albumin/Creatinine Ratio in Non-Obese Non-Diabetic Patients with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition seen as histological change ranging from simple steatosis to steatohepatitis, advanced fibrosis and liver disease among patients without significant alcohol consumption. Microalbuminuria which is defined as the urinary albumin excretion of 30 - 300 mg/24h has been reported to be a risk factor for renal and cardiovascular disorders. It also has independent correlation to high mortality in diabetic and hypertensive patients. NAFLD is affecting non obese non diabetic individuals;Microalbuminuria is correlated to visceral adipose tissue even in non diabetic non obese patients with limited studies in this aspect. Microalbuminuria is considered as a risk factor for cardiovascular and chronic kidney disease. Aim of the work: To assess urinary albumin creatinine ratio in non-obese non-diabetic patients with nonalcoholic fatty liver disease. Patients and methods: Total number of 80 patients with NAFLD that were non diabetic non obese patients. Abdominal ultrasonography and laboratory investigations were done. Results: Eighty non-obese, non-diabetic subjects (32 women, 48 men) with the mean age of 50.9 were included in this study. The population of the study was classified into four groups according to ultrasonographic degrees of steatosis. Control Group (A), (No. 25) 31.25% of total cases are reported as no fat accumulation in liver. Group B;No. 21 26.25% of total cases are reported as had mild steatosis (NAFLD 1). Group C;No. 18 (22.5%) of total cases and reported as had moderate fat accumulation (moderate steatosis). Group D;No. 16 (20%) of total cases reported had severe fat accumulation (severe steatosis). Urinary albumin creatinine ratio also shows increase in its values with increasing in the degree of steatosis among different groups which is highly statistically significant. Triglycerides, total cholesterol and LDL show also significant changes between groups as they are significantly increased in value as regard increasing in degree of steatosis, inversely noticed with HDL levels as it goes down with elevated degree of steatosis which is statistically significant. Discussion: The effects of fatty liver disease on renal functions have been evaluated in some studies;in this study we tried to evaluate the correlation between microalbuminuria and various degrees of steatosis in non-obese non diabetic patients;we found that NAFLD could be seen in non obese non diabetic individuals with special reference to other factors that may influence the progress of the disease such as hyperlipidemia with increased risk of microalbuminuria among those patients. Conclusion: After exclusion of type 2 DM and obesity, we conclude that the presence and the severity of microalbuminuria are more apparent among NAFLD patients.

山莴苣素调控线粒体功能改善FFA诱导HepG2细胞脂质堆积及抗NAFLD的作用研究

研究山莴苣素通过调控线粒体功能对游离脂肪酸(FFA)诱导HepG2细胞脂质堆积的影响,探索抗非酒精性脂肪肝病(NAFLD)机制。FFA诱导HepG2细胞脂质变性(构建NAFLD体外模型),给予山莴苣素共同处理48 h。采用油红O染色观察细胞内脂滴含量,检测细胞内甘油三酯(TG)含量,脂肪酸β氧化的活力以及高通量电子显微镜观察MitoSOX Red与Mitotracker Red的荧光强弱;qRT-PCR法检测脂质代谢与线粒体相关基因的相对表达量;蛋白质印迹法测定PPARα的蛋白水平。结果显示,与模型组相比,山莴苣素抑制FFA诱导HepG2细胞内脂滴的增加,降低TG含量、MitoSOX Red的荧光强度以及SREBP1的mRNA相对表达量;上调脂肪酸β氧化的活力、Mitotracker Red的荧光强度以及AMPK、PPARα、CPT1A、PPARγ、PINK1、Parkin基因的相对表达量和PPARα蛋白表达水平。山莴苣素通过PPARα/CPT1A,PINK1/Parkin的信号转导恢复线粒体功能,改善FFA诱导HepG2细胞脂质堆积。

基于ERS信号蛋白异常表达探讨清肝降浊方治疗NAFLD的机制研究

目的通过试验研究探讨清肝降浊方基于ERS信号蛋白异常表达治疗非酒精性脂肪肝病的作用机制。方法采用高脂饮食饲喂的方法,诱导建立非酒精性脂肪肝病大鼠动物模型。给药8周后,进行肝功能指标AST、ALT、AKP检测、血清中TC、TG、NEFA及肝组织匀浆中TC、TG检测、肝组织匀浆中SOD、MDA检测,检测信号通路相关蛋白ATF4、eIF2a、CHOP的表达水平。结果清肝降浊方865.1 mg/kg、432.6 mg/kg和216.3 mg/kg给药组动物血清AST、ALT、AKP活性及肝组织中ATF4、CHOP表达量、TG含量均明显的低于模型组,而肝组织中SOD活性显著高于模型组(P<0.01或P<0.05);865.1 mg/kg和432.6 mg/kg 2个给药组动物血清TC、TG、NEFA含量及肝组织中TC、TG、MDA含量、eIF2a表达量均低于模型组(P<0.01或P<0.05)。结论清肝降浊方治疗NAFLD作用机制可能是通过调节ERS信号蛋白异常表达,从而达到防治非酒精性脂肪肝病。

基于UPLC-Zone TOF-MS/MS联合网络药理学探讨脉复生防治NAFLD作用

依据脉复生的化学成分,采用网络药理学、分子对接技术、构建NAFLD小鼠模型,探究脉复生防治NAFLD的作用机制。通过UPLC-Zone TOF-MS/MS对脉复生全成分进行检测;借助Swiss生物信息学研究平台获取活性成分和靶点,在OMIM、Disgenet数据库筛选NAFLD疾病靶点,对交集靶点进行PPI分析;在Metascape网站进行GO与KEGG富集分析,对核心靶点与活性成分展开分子对接;采用HFD诱导C57BL/6J小鼠构建NAFLD模型进行核心靶点验证;指认得到130个化学成分,筛选得到54个活性成分与176个可能作用于NAFLD的潜在靶点;根据Degree值对排名前10的成分与靶点进行分子对接实验,对结合能最优的对接模型TNF与Quercetin、IL-17与Asiatic acid、IL-1β与Quercetin进行可视化分析;筛选炎症因子和脂肪代谢相关基因进行qPCR测序。富集分析表明脉复生治疗NAFLD与脂肪酸转化、脂质代谢正向调节等生物过程相关,涉及AGE-RAGE、HIF-1、IL-17等信号通路;与对照组相比,模型组血清学检测ALT、TG、LDL-C指标上升并且HDL-C指标下降(P<0.05);与模型组相比,脉复生给药组和辛伐他汀组能够降低小鼠体质量、肝脏和脂肪质量占比(P<0.05),降低血清中TNF-α、IL-1β和IL-17的含量和mRNA表达,在高剂量时具有显著性差异(P<0.01);与对照组相比,脉复生给药组能够通过调节脂质代谢相关基因的表达,降低肝脏脂质堆积,缓解肝脏脂肪变性。

Metabolic syndrome in metabolic obese, non-obese elderly in northern Taiwan

Background: The prevalence of metabolic syndrome is high in non-obese adult individuals, but less research focusing on elderly group. We aimed to assess the prevalence rates of metabolic syndrome (MetS) and its individual components in metabolic obese, non-obese elderly population in northern Taiwan (body mass index [BMI] 2). Methods: A cross-sectional survey was conducted among elderly people (≥65 y/o) who received a senior citizen health examination from March to November 2009. A total of 1180 participants (433 men, 36.7%;748 women, 63.3%) were investigated. The prevalence and odds ratios of metabolic syndrome, as defined by the modified Adult Treatment Panel III (ATP III), were analyzed in the following BMI groups: 2, 18.5 - 24 kg/m2, 24 - 27 kg/m2, and ≥27 kg/m2. Results: The prevalence of metabolic syndrome increased with BMI in both women and men (P 2, and 1.09 (1.02 - 1.17) for men with BMI 24 - 27 kg/m2. Conclusions: Elderly individuals in the BMI belong to normal and overweight groups have a relatively high prevalence and increased risk of developing MetS. Therefore, physicians should perform screening examinations for MetS and its risk factors not only in obese patients but also in non-obese elderly patients to prevent Mets. This electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.

Evaluation of Lipid Profile in Obese and Non-Obese Hypertensive Adult Patients Attended in Medicine Department of a Medical College Hospital of Bangladesh

Background: By the dawn of this modern era of science, the prime challenge of physician is cardiovascular disease (CVD). The most important modifiable risk factors of CVDs are unhealthy diet, physical inactivity and tobacco use. The effects of unhealthy diet and physical inactivity include abnormal blood lipid, obesity and hypertension. We tried to evaluate and correlate the pattern of lipid profile in obese and non-obese hypertensive patients. Objectives: This study was conducted at medicine department of Cumilla Medical College Hospital. The principal aim was to evaluate the lipid profile in obese and non-obese adult hypertensive patients. Methodology: During this cross sectional analytical study, a total of 100 adult hypertensive patients were taken by purposive sampling. Among them 50 (group 1) patients were taken those were obese and 50 (group 2) patients taken those were non-obese according to BMI measurement on operational definition. Diagnosis of hypertension would be established with the help of ambulatory BP measurements two occasions few minutes apart. The staging of hypertension was done according to JNC7 Criteria. Morning blood samples were taken after 8 - 12 hours of fasting and lipid profiles were done on authentic laboratories. The laboratory values were interpreted according to the operational definition of dyslipidaemia. The ethical research and review committee approved the study protocol and signed informed consent was obtained from the participants. The statistics was analyzed using the IBM SPSS software of version 19.0. Statistical significance was set at p < 0.05. Results: Among the two groups, there were 56 (56%) males and 44 (44%) females. The mean age of group 1 (46.10 ± 11.09) was compared to that of group 2 (45.5 ± 10.6). Lipid profile abnormalities were significantly higher in the stage 2 hypertension (59.62%) and stage 3 hypertension (66.66%), higher in class 2 obese (100%) and class 3 obese subjects (100%), female hypertensive patients had significantly higher BMI than their male counterparts (27.24 ± 3.63 kg/m2 versus 29.29 ± 3.99 kg/m2), lipid profiles were higher in the female than male hypertensive patients (63.33% vs 55.35%) but only TC was statistically significant (4.45 ± 1.19 mmol/l versus 4.86 ± 1.29 mmol/l, p < 0.05). Those who were obese had significant high TG (p < 0.001), high TC (p < 0.001) and high LDL-C (p < 0.001). 38 (76%) of the obese hypertensive patients had dyslipidaemia whereas 21 (42%) of non-obese hypertensive patients had dyslipidaemia. In multivariate regression, TG was significantly and directly associated with BMI of subjects. Dyslipidaemia was more prevalent in the age group 30 - 59 of adult hypertensive patients. It showed that obese hypertensive patients had significantly higher SBP (p < 0.001), DBP (p < 0.001) than non-obese subjects. The mean TC (4.83 ± 0.95 mmol/l versus 4.15 ± 0.57 mmol/l, t = -9.70, p < 0.001), TG (2.64 ± 0.67 mmol/l versus 2.10 ± 0.45 mmol/l, t = -5.37, p < 0.001) and LDL-C (3.00 ± 0.82 mmol/l versus 2.44 ± 0.53 mmol/l, t = -9.11, p < 0.001) were also significantly higher among the hypertensive obese subjects. The mean HDL-C was however comparable in the two groups (1.25 ± 0.27 mmol/l versus 1.24 ± 0.57 mmol/l, t = -0.25, p = 0.08)...

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.

科罗索酸调控FGF15逆转NAFLD抑制ALPPS诱导肝再生的研究

联合肝脏分隔和门静脉结扎二步肝切除术(ALPPS)是肝脏外科领域的新技术,为剩余肝体积(FLR)过小的病人提供再次手术机会,改善了手术的制约性[1]。脂肪肝病人经历肝脏大部切除术后肝脏体积恢复较慢,发生并发症及死亡率的风险较高[2],另外,动物实验研究表明,非酒精性脂肪肝(NAFLD)降低了ALPPS术后肝脏再生能力[3]。

基于脂质组学探究游泳运动对NAFLD小鼠脂质代谢的改善作用

目的 探究游泳运动(SE)对非酒精性脂肪性肝病(NAFLD)小鼠脂质代谢的调节作用。方法 将27只C57BL/6J小鼠分为对照组(正常饮食)、高脂饮食(HFD)组和HFD+SE组,每组9只。12周后取肝组织进行基于LC-MS的非靶向脂质组学检测。通过建立OPLS-DA模型对脂质组学数据进行多维统计分析,并结合t检验,筛选出样本中OPLS-DA VIP>1和P<0.05的代谢物作为显著性差异脂质化合物。结果 HFD组与对照组比较,有81种差异脂质化合物;HFD+SE组与HFD组比较,有27种差异脂质化合物。差异脂质化合物主要归属于甘油酯类、甘油磷脂类和鞘脂类。结论 NAFLD小鼠脂质代谢谱发生改变,游泳运动对NAFLD小鼠脂质代谢具有改善作用。

他汀类药物联合多奈哌齐治疗NAFLD合并AD的疗效及对LCN2的影响

目的:探讨他汀类药物联合多奈哌齐治疗NAFLD合并AD的疗效及对LCN2的影响。方法:选择本院2021年1月—2023年6月收治的66例NAFLD合并AD患者为研究对象,按电脑随机法分组,分为观察组(33例)和对照组(33例);对照组给予多奈哌齐治疗,观察组在对照组基础上加用他汀类药物,比较两组治疗效果。结果:治疗后,观察组患者的氧化应激指标(MDA、SOD)对比具有显著差异(P<0.05),且观察组患者的SOD水平更高,MDA水平更低(P<0.05);治疗后,观察组ADL和MMSE评分高于对照组(P<0.05);治疗后,两组患者的LCN2水平明显降低,且观察组患者的LCN2指标低于对照组(P<0.05);治疗后,两组患者的不良反应发生率(6.06%VS18.18%)对比差异不大(t=2.276,P=0.131)。结论:在他汀类药物联合多奈哌齐治疗NAFLD合并AD的疗效十分显著,可加以应用和推广。

虎杖活性成分及其方药治疗NAFLD的研究进展

虎杖具有清热解毒、止咳化痰等功效,可用于高血脂、痛风性关节炎、病毒性感染疾病、呼吸系统疾病等的治疗。研究表明,虎杖治疗NAFLD活性成分主要包括二苯乙烯类、蒽醌类、黄酮类,其作用机制主要体现在改善脂质过氧化、降血脂、改善肝功能及改善炎症反应等方面。现对近年来相关研究中所提到的虎杖及其类方药的临床应用、药理研究、治疗NAFLD活性成分等进行系统综述。

Limosilactobacillus mucosae FZJTZ26M3 prevents NAFLD in mice through modulation of lipid metabolism and gut microbiota dysbiosis

Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.

肝线粒体在NAFLD中的病理变化及中药辨证干预的实验研究

目的:探讨肝线粒体在NAFLD发病过程中的超微病理变化及中医辨证治疗的影响。方法:取SPF级Wistar大鼠40只,随机分为5组。造模并干预给药,于实验第12周时,处死大鼠,取肝组织制作肝脏的超微病理切片,观察各组肝细胞线粒体的病理变化及中药辨证干预的影响。结果:肝细胞线粒体在各造模组中有不同程度的病理改变。在12周时,药物B方保护肝线粒体的疗效较其他干预措施为优。结论:在NAFLD的后期采取化痰消瘀、清热利湿、补益肝肾治法对于保护肝细胞线粒体疗效突出。

GLP-1对NAFLD大鼠肝功能及TLR4/NF-κB信号通路的影响

目的研究胰高血糖素样肽-1(GLP-1)对非酒精性脂肪性肝病(NAFLD)大鼠肝功能及TLR4/NF-κB信号通路的影响。方法将45只大鼠随机分成两组,正常饲料喂养15只,高脂饮食喂养30只使其形成NAFLD模型。在第10周,把高脂饲料喂养的28只老鼠随机分成两组,模型对照组(14只)和GLP-1干预组(14只);正常饲料喂养的15只为正常对照组。之后对模型对照组和正常对照组大鼠进行注射生理盐水处理,GLP-1干预组大鼠注射利拉鲁肽处理;期间查看大鼠的活动、体质量、食欲、大小便等情况的变化。结果与正常对照组相比,模型对照组的大鼠其肝指数、肝质量、ALT、AST、TG、TC均明显升高(P<0.05),与模型对照组对比,GLP-1干预组大鼠的肝指数、肝质量、ALT、AST、TG、TC均明显下降(P<0.05);与正常对照组比较,模型对照组的TLR4和NF-κB蛋白表达上升(P<0.05),GLP-1干预组和模型对照组比较,TLR4和NF-κB蛋白的表达降低(P<0.05)。结论 GLP-1可明显扭转NAFLD大鼠的糖脂代谢絮乱和肝功能受损的情况,GLP-1可明显降低大鼠肝组织中TLR4和NF-κB的蛋白表达。

SIRT1信号通路在高尿酸介导的NAFLD大鼠中的表达及白藜芦醇的干预作用

[目的]探讨白藜芦醇对高尿酸介导的非酒精性脂肪性肝病(nonalcholic fatty liver disease,NAFLD)大鼠血清炎症指标的影响及病理学的改变。[方法]采用改良的高酵母高脂饲料喂养,合并氧嗪酸皮下注射,建立高尿酸介导的NAFLD大鼠模型。36只SPF级雄性SD大鼠,随机分为3组:正常对照组、模型组、白藜芦醇治疗组,每组12只。分别观察白藜芦醇对NAFLD伴高尿酸大鼠体质量、肝湿重、血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、门冬氨酸氨基转移酶(aspartate transaminase,AST)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白介素6(interleukin6,IL-6)、尿酸(uric acid,UA)含量的影响,并与正常对照组、模型组比较分析病理学变化,免疫组化检测沉默信息调节因子1(silent information regulator 1,SIRT1)、环氧化酶2(cyclooxygenase-2,COX-2)、核转录因子κB(nuclear factor kappa B,NF-κB)表达情况。[结果]白藜芦醇治疗后,高尿酸介导的NAFLD大鼠肝湿重低于模型组,差异有统计学意义(P<0.05),血清ALT、AST、TNF-α、IL-6、UA含量降低,差异有统计学意义(P<0.01),肝组织病理显示脂肪变性及炎性反应较模型组减轻。与模型组比,白藜芦醇治疗组大鼠肝组织中COX-2、NF-κB表达均减弱,差异有统计学意义(P<0.01),SIRT1表达增强,差异有统计学意义(P<0.01)。大鼠肝脏脂肪变性和炎症评分与COX-2、NF-κB表达之间存在正相关,与SIRT1表达之间存在负相关(P<0.01)。COX-2、NF-κB与SIRT1表达之间存在负相关(P<0.01)。[结论]白藜芦醇通过促进伴随高尿酸的NAFLD肝细胞中SIRT1表达,抑制COX-2表达和NF-κB转录活性,阻止炎症细胞因子(如TNF-α、IL-6)介导的细胞毒效应,减轻炎症程度从而发挥治疗NAFLD的作用。

中医辨证治疗对NAFLD大鼠血脂等影响的实验研究

目的:探讨中医辨证治疗对非酒精性脂肪性肝病(NAFLD)大鼠各时期血脂等指标影响的作用机制,为临床防治NAFLD提供理论依据。方法:取SPF级Wistar大鼠72只,雌雄各半,随机分为正常组、模型组、对照药物治疗组、药物A方治疗组、药物B方治疗组、先A方后B方治疗组、先B方后A方治疗组、先空白后A方治疗组、先空白后B方治疗组,共9组。除正常组给予普通饲料外,其余各组均饲以高脂饲料。造模第4周后,模型组加用生理盐水灌胃;对照组加用对照药物灌胃;药物A方组加用治疗药物A方灌胃;药物B方组加用治疗药物B方灌胃;先A方后B方治疗组即4～8周用A方,8～12周用B方灌胃;先B方后A方治疗组即4～8周用B方,8～12周用A方灌胃;先空白后A方治疗组即先空白,第8～12周用A方灌胃;先空白后B方治疗组即先空白,第8～12周用B方灌胃。实验第12周时,测定大鼠血清TCH、TG、HDL、LDL、FFA、GSH-ST、TNF-α的值。结果:实验第12周时,先A方后B方治疗组(编号为6组)降低NAFLD后期大鼠血清TG、TCH、LDL、FFA、TNF-α及升高血清GSH-ST水平的疗效与其他治疗组相比尤为显著(P<0.01或P<0.05)。结论:在NAFLD的整个病程中,采取早期阶段运用疏肝健脾、活血化瘀、化痰利湿功效的治法,后期阶段运用化痰消瘀、清热利湿、补益肝肾功效的治法的治疗方案,对于降低大鼠血脂等指标及提高大鼠抗氧自由基的疗效显著优于其他治疗措施。

瘦素和多囊卵巢综合征(PCOS)伴非酒精性脂肪肝(NAFLD)相关性的临床观察

目的通过对多囊卵巢综合征(polycystic ovary syndrome,PCOS)人群中伴非酒精性脂肪肝(non-acoholic fatty liver disease,NAFLD)的分析,探讨瘦素与PCOS伴NAFLD之间的关系。方法收集35例PCOS伴有NAFLD的患者为脂肪肝组,同期选择35例PCOS不伴NAFLD的患者为非脂肪肝组,健康女性志愿者20例为对照组。所有受试者进行相关问卷调查建立个人病例档案,测量身高(height,H)、体重(weight,W)、体重指数(body mass index,BMI)、腰围(waist circumference,WC)、臀围(hip circumference,HC)及腰臀比(wasit hip ratio,WHR);检测血清睾酮(testosterone,T)、泌乳素(prolactin,PRL)、卵泡刺激素(folliclestimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、雌二醇(estradiol,E2)、瘦素、空腹血糖(fasting blood sugar,FBG)、空腹胰岛素(fasting insulin,FINS)、餐后2h血糖(2hpostprandial blood glucose,2hPBG)、稳态模型胰岛素抵抗指数(homeostatic model assessment for insulin resistance,HOMA-IR)、总胆固醇(total cholesterol,TC)、三酰甘油(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)及丙氨酸转氨酶(alaninetransaminase,ALT)等指标。结果两组PCOS的瘦素、W、BMI、WHR、T、LH、LH/FSH、FINS、PBG、HOMA-IR、LDL-C各项指标均高于对照组(P<0.05),FSH显著低于对照组(P<0.05);而PCOS伴NAFLD的瘦素、W、BMI、WC、HC、WHR、FINS、PBG、HOMA-IR、TG、LDL-C、ALT较不伴NAFLD显著升高(P<0.05),HDL-C显著降低(P<0.05)。脂肪肝组的瘦素水平与年龄、W、BMI、WC、HC、WHR、FINS、HOMA-IR及TG呈均显著正相关性(P<0.01),与HDL-C呈显著负相关性(P<0.01),控制与体脂有关的如W、BMI、WC、HC、WHR,脂肪肝组的瘦素水平与HOMA-IR、TG仍有显著正相关性(P<0.01)。结论瘦素水平异常与PCOS伴NAFLD的形成密切相关,及早重视瘦素干预,对于防治PCOS伴NAFLD有重要意义。

骨钙素(OCN)与非酒精性脂肪肝(NAFLD)关系的研究进展

骨钙素(osteocalcin,OCN)是由成骨细胞生成并特异性分泌的非胶原蛋白,参与调节胰岛素分泌、葡萄糖代谢和能量消耗,成为骨和调节能量代谢器官的复杂信号通路之间的重要话串的关键分子。肝脏作为代谢中枢器官参与多种物质代谢。动物及细胞分子学实验显示,OCN具有改善肝脏脂肪过量沉积的作用,其机制可能与OCN降低血清三酰甘油水平、促进胰岛素分泌、改善胰岛素抵抗、减轻氧化应激及炎性反应等相关。多项临床研究表明,OCN与糖代谢、脂代谢、肥胖等代谢异常密切相关,但OCN与非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的关系研究目前仍存在争议。

二甲双胍通过调节FGF21/adiponectin轴改善NAFLD大鼠脂代谢紊乱

目的探讨二甲双胍通过调节FGF21/adiponectin轴改善高脂诱导NAFLD大鼠脂代谢紊乱的作用。方法将25只SD大鼠予以高脂饮食喂养8周后,取5只证实NAFLD模型建立;继将剩余20只大鼠分为模型组(HF组)、二甲双胍干预组(HF+M组),每组10只,并继续给予高脂饮食;另取10只普通饮食饲养大鼠作为对照组(NC组)。于灌胃8周末,应用全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)及空腹血糖(FBG);酶免法测定肝脏TG含量、血清胰岛素(FINS)、成纤维细胞生长因子(FGF21)及脂联素(Adiponectin)水平,并计算胰岛素抵抗指数(HOMA-IR);HE染色光镜下观察大鼠肝细胞脂肪变性情况;采用Real-time PCR法检测肝组织FGF21、AMPK mRNA表达及脂肪组织adiponectin mRNA表达。结果与NC组比较,HF组大鼠出现糖脂代谢紊乱及轻度肝功能受损,伴明显胰岛素抵抗、肝脏TG过度沉积及血清Adiponectin水平下降;二甲双胍干预后,可降低HF组大鼠血清TC、TG、FBG、ALT、AST、肝脏TG含量及HOMA-IR(P<0.05),升高血清adiponectin及FGF21水平;HE染色提示肝脏脂肪变较模型组明显好转;与HF组比较,二甲双胍可增加肝脏AMPK-α及FGF21 mRNA表达(P<0.05),而adiponectin mRNA表达无明显变化(P>0.05),但脂肪组织adiponectin mRNA表达明显上调。结论与高脂喂养组比较,二甲双胍可有效减轻高脂诱导大鼠肝脏脂质沉积及外周胰岛素抵抗,推断其机制与二甲双胍通过AMPK途径上调肝脏FGF21 mRNA表达有关,但其并非直接作用于肝细胞,可能是通过刺激脂肪组织adiponectin分泌而发挥降脂及改善胰岛素抵抗的作用。