Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

AIM： To investigate oxidative stress and lipid peroxi-dation in hepatic steatosis and the underlying implica-tions in pathological mechanisms of non-alcoholic fatty liver disease （NAFLD）. METHODS： F2-isoprostanes （iPF2α-） in blood and liver samples from steatotic （n = 9） and control （n = 7） rats were measured as in vivo marker of lipid peroxida-tion by a mass spectrometric approach. The lipid pro-fi le and endogenous antioxidant status （SOD and CAT） in the rats were also analyzed. RESULTS： Signifi cantly higher levels of iPF2α-（mean 3.47 vs 2.40 pmol/mg tissue, P = 0.004） and lower activities of SOD （mean 1.26 U vs 1.40 U, P 〈 0.001） and CAT （mean 1026.36 U/mg vs 1149.68 U/mg pro-tein, without signifi cance） were observed in the livers of steatotic rats. Plasma total iPF2α-was signifi cantly correlated with the abnormalities of blood lipids as well as alanine aminotransferase （ALT） levels in the rats with simple steatosis, whereas no similar tendencies were observed in the control rats. CONCLUSION： Enhancement of hepatic oxidative imbalance occurring at the steatotic stage of NAFLD suggests a possibility that manifestation of the local ⅢⅢⅢoxidative damage precedes that of systemic oxidative imbalance. Predominant metabolic features of the in-creased lipid peroxidation further suggest a close asso-ciation of the oxidative imbalance and the dyslipidemia with functional deterioration of the steatotic liver. The fi ndings need to be further evaluated, especially in hu-man studies.     

活动性炎症性肠病患者蛋白质和脂代谢的变化

目的 比较炎症性肠病患者及正常对照者之间蛋白质和脂代谢的差异,研究这些差异与疾病活动性及病变部位的关系.方法 回顾性研究1995至2007年溃疡性结肠炎(UC)195例、克罗恩病(CD)76例及正常对照者97名的蛋白质和脂代谢资料.同时评价临床疾病活动指数,红细胞沉降率(ESR)和C-反应蛋白(CRP)水平.性别分层分析蛋白质和脂代谢指标的改变,同时分析蛋白质和脂代谢的改变与疾病活动性及病变部位的关系.结果 UC患者的ESR与血清白球比呈负线性相关(β=-0.521,P＜0.01),与α2-球蛋白呈正线性相关(β=0.319,P＜0.01);CD患者血清球蛋白与ESR(β=0.558,P＜0.01)以及cRP(β=0.424,=P0.01)呈正线性相关.UC患者间因病变部位不同,血清白球比、白蛋白和总胆固醇水平存在显著差异,其中直乙结肠炎患者该三项显著高予其他类型的UC患者(P值分别=0.003、0.005、0.038).CD患者间亦因病变部位不同,血清球蛋白水平存在显著差异,仅累及结肠者的血清球蛋白水平显著高于单纯小肠受累者(P=0.029).结论 UC患者血清白球比和α2-球蛋白的异常程度可作为炎症活动性的预测因素;CD患者血清球蛋白增高预示疾病严重程度活动性增加,累及小肠的CD患者相对仅累及结肠的CD患者而言存在更为严重的营养缺失.     

自噬在肝脏脂质代谢中的意义及其与胰岛素抵抗的关系

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗、脂质代谢紊乱、慢性炎症以及遗传易感性强烈关联的获得性代谢应激性肝损伤,疾病谱包括单纯性脂肪肝、脂肪性肝炎及其相关纤维化、肝硬化。由于肥胖症和代谢综合征在全球的流行,近20年亚洲国家和地区NAFLD增长迅速,导致疾病谱变迁,NAFLD现已成为欧美发达国家(流行率17%~33%)以及我国经济较发达地区的第一大慢性肝病。近几年研究发现,自噬作为一种细胞程序,在介导脂质代谢过程中具有非常关键的作用,结合NAFLD的流行病学、发病机制,本文就自噬在肝脏脂质代谢中的作用意义及其与IR的关系研究现状作一综述。     

Acupuncture improved lipid metabolism by regulating intestinal absorption in mice

BACKGROUND Non-alcoholic fatty liver disease(NAFLD), in which abnormal lipid metabolism plays an important role in disease progression, has become a pandemic. r Abnormal lipid metabolism, for example an increased fat intake, has been thought to be an initial factor leading to NAFLD. The small intestine is the main site of, dietary lipid absorption. A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism, which is closely associated with the progression of NAFLD. We therefore hypothesized that, acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of lipid.AIM To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse model.METHODS 8-wk-old male C57 BL/6 J mice were fed a methionine-and choline-deficient diet for 3 wk. Then, all mice were separated randomly into acupoints group(AG) or non-acupoints group(NG) with high fat diet feeding. Needling treatment was performed at Zu san li, Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG mice. Finally, mice were anesthetized with an injection of ketamine-medetomidine and euthanized by exsanguination.RESULTS An apparent improvement of obesity was found in AG mice after acupuncture treatment. In AG mice, the body weight was much lower(22.6 ± 1.2 g vs 28.1 ± 1.0 g, P 0.005) in comparison to NG mice. The length of small intestine in AG mice was significantly shorter(26.7 ± 2.3 cm vs 32.7 ± 2.7 cm, P 0.005). A large amount of chyme was observed in the lumen of the AG small intestine. The expression of microsomal triglyceride transfer protein, apolipoprotein B and apolipoprotein C2 was downregulated. Triacylglycerols(TGs), total cholesterol and nonesterified fatty acid(NEFA) levels of the small intestinal tissue were significantly higher in AG mice, but the serum TGs and NEFA levels were reduced in AG mice.CONCLUSION These results indicate that acupuncture at Zu san li, Guan yuan and Yong quan suppressed lipid absorption by downregulating the expression of apolipoproteins in the small intestine.     

环境新兴污染物双酚A暴露加重非酒精性脂肪性肝病大鼠脂质代谢异常*

目的探讨在非酒精性脂肪性肝病（NAFLD）背景下新兴环境污染物双酚A（BPA）对机体脂质代谢的影响。方法将18只SD大鼠随机分为正常饮食组、高脂饮食（NAFLD）组和NAFLD/BPA处理组,饲养12 w。采用Western blot法检测血清和肝组织脂代谢相关蛋白的变化。结果NAFLD组和NAFLD/BPA组肝质量分别为（20.5±2.8）g和（20.9±1.9）g、体质量为（500.1±19.1） g和（511.1±20.5） g、血清甘油三酯分别为（2.5±0.5）mmol/L和（2.8±0.9）mmol/L、胆固醇为（2.4±0.7）mmol/L和（2.8±0.6）mmol/L,游离脂肪酸（FFA）分别为（578.6±48.7）mmol/L和（602.2±50.3）mmol/L,均显著高于正常组【（15.2±2.3）g、（432.5±13.2）g、（2.0±0.8）mmol/L、（1.0±0.6）mmol/L和（487.4±14.9）mmol/L,P<0.05】;与正常组比,NAFLD组和NAFLD/BPA组肝组织脂肪酸合成酶（FAS）分别上调了2.45倍和1.91倍,靶基因乙酰辅酶A合成酶（ACS）蛋白表达量分别下降了1.54倍和1.5倍（P<0.05）。结论BPA的长期摄入可加重机体肥胖,促进血脂异常。     

锌对免血栓素前列腺环素及脂代谢的影响

目的　探讨锌对血栓素 B2 (TXB2 )、6 -酮 -前列腺环素 F1α(6 - keto- PGF1α)、脂代谢及抗氧化功能的影响。方法　纯系新西兰雄性大白兔 2 0只 ,分为对照组和加锌组 ,加锌组饮水中加葡萄糖锌 (锌浓度 15 .3 mm ol/L )。实验前后 3次观察 TXB2 、6 - keto- PGF1α、超氧化物歧化酶 (SOD)、脂质过氧化物 (L PO)、血清总胆固醇 (T、C)、脂蛋白 (L DL- C、HDL- C)、载脂蛋白 (Apo B1 0 0 、Apo AI)变化。结果　加锌组血清锌在补锌后持续升高 (P <0 .0 1) ,心、肝、肾、肌肉锌也升高 (P <0 .0 5或 0 .0 1)。血液及组织 SOD活性下降 (P <0 .0 5或 0 .0 1) ,L PO含量升高 (P <0 .0 5或 0 .0 1) ,血液及肝 SOD/ L PO比值变小 (P <0 .0 1)。TC、L DL- C、Apo B1 0 0 较实验前及对照组升高 (P<0 .0 5或 0 .0 1) ,HDL- C、Apo AI降低 (P <0 .0 5或 0 .0 1)。 TXB2 较实验前及对照组升高 (P <0 .0 1) ,6 - keto-PGF1α3个月时有升高趋势 ,6个月明显降低 (P <0 .0 1)。结论　高锌摄入能升高 TXB2 ,降低 6 - keto- PGF1α,干扰脂代谢 ,抑制抗氧化功能     

鼠李糖乳杆菌干预肠道菌群及脂质代谢治疗代谢相关性脂肪性肝病的研究进展

代谢相关性脂肪性肝病(metabolic associated fatty liver disease, MAFLD)现已成为全世界最常见的慢性肝病,发病率在逐年增加,目前无临床特效药,其发病机制复杂,主要涉及肥胖、肠道菌群、胰岛素抵抗、环境、遗传等。近年来,益生菌在预防和治疗MAFLD中被广泛研究,鼠李糖乳杆菌(Lactobacillus rhamnosus, LGG)属乳杆菌属的经典益生菌菌株。大量研究证明,LGG可通过调节肠道菌群、改善肠黏膜屏障及降低胆固醇改善MAFLD。本文主要阐述LGG干预MAFLD的相关可能机制。     

胡桃苷对非酒精性脂肪性肝小鼠中肝脂质代谢紊乱、肝损伤以及小肠完整性的改善作用

背景现有研究对胡桃苷在非酒精性脂肪性肝病(nonalcoholicfattyliverdisease,NAFLD)中的治疗作用尚未得到充分关注.目的本研究通过高脂饮食(high fatty diet, HFD)小鼠模型评估了胡桃苷在NAFLD中的治疗效果.方法C57B L/6小鼠分为标准饮食组、H F D组、胡桃苷低、中和高剂量治疗组.给药方案结束后,采集小鼠血样和组织(肝和小肠)进行生化及组织学测定.结果胡桃苷抑制了HFD诱导的肝组织形态学改变和肝脂质沉积,并降低了血清中谷草转氨酶、谷丙转氨酶和胆固醇含量以及葡萄糖、血清胰岛素水平和胰岛素抵抗稳态模型值.胡桃苷显著改善了HFD引起的代谢损伤,增加了肝脏过氧化物酶体增殖体激活受体及其下游调节基因成纤维细胞生长因子21的m RNA水平,并且提高了乙酰辅酶A羧化酶的磷酸化水平和肉碱-棕榈酰基转移酶的m RNA水平.此外,胡桃苷还减少了肝脏炎症,恢复了肠道屏障的完整性和功能(FITC-dextran通透性下降和小肠组织紧密连接蛋白1表达增加).结论胡桃苷可恢复NAFLD引起的脂肪变性、减少肝脏炎症、恢复葡萄糖稳态和改善肠道完整性.     

人参皂苷对脂代谢的调控作用

人参总皂苷或人参皂苷(GS)单体可通过多种机制改善脂代谢,主要包括:通过下丘脑腹内侧核抑制摄食行为;通过下调胰脂肪酶(PL)活性,抑制肠道含脂食物吸收;抑或通过调控脂肪生成转录因子过氧化物酶体增殖物活化受体(PPARs)、糖脂代谢调控分子腺苷酸活化蛋白激酶(AMPK)及其靶基因表达等.     

肥胖症与脂质代谢

肥胖是一种常见疾病，是体内脂肪过多的表现，与脂质代谢紊乱密切相关，二者互为因果。其脂质代谢紊乱表现为摄食过多使脂肪合成的原料增加，棕色脂肪含量减少使能量消耗减少素和降脂激素调节失常使脂肪合成增加，降解减少。同时也可由于脂肪动员增加使血中游离脂肪酸，甘油三酯增加，极低密度脂蛋白和低密度脂蛋白清除减少。高胰岛素血症和胰岛素抵抗既是肥胖的结果，也是肥胖患者脂质代谢紊乱的主要原因，其它如瘦素等也起重要作用。     

三磷酸腺苷结合盒转运子A7在脂质转运过程中作用的研究

目的:探讨三磷酸腺苷结合盒转运子A7(ABCA7)在细胞内脂质流出过程中的作用。方法:以apoAI刺激转染ABCA7-或ABCA1-基因的HEK293细胞24h,利用蛋白印迹法以及酶分析法分别测定ABCA7的变化与细胞内胆固醇和磷脂的流出。结果:apoAI分别上调ABCA7或ABCA1蛋白量,ABCA7与ABCA1同样促进细胞内脂质的转运,其中磷脂的流出较胆固醇流出更为明显。结论:ABCA7与ABCA1同样具有促进细胞内脂质转运的功能。     

载脂蛋白E多态性与冠心病患者脂代谢的临床研究

目的研究载脂蛋白E(apoE)多态性与冠心病(CHD)及其脂代谢之间的关系。方法采用等电点聚焦电泳免疫印迹技术测定91例CHD及105例正常对照者的apoE表型,并用酶法测定他们的脂质水平。结果CHD组和对照组apoE表型分布及等位基因频率无显著性差异(P＞0．05)。CHD组不同apoE表型之间血脂水平比较发现,apoE基因多态性与胆固醇(TC)(P＜0．01)、低密度脂蛋白胆固醇(LDL-C)(P＜0．01)、甘油三酯(TG)(P＜0．05)有关,即E4等位基因携带者具有较高的TC和LDL-C水平,而E2等位基因携带者具有较低的TC和LDL-C水平。E2和E4等位基因携带者TG水平均升高。结论apoE基因多态性影响CHD患者的脂代谢,并通过影响脂代谢在CHD中起重要作用,但不是CHD的一个独立危险因素。     

有机铬对实验性糖尿病大鼠糖、脂质代谢的影响

目的:观察微量元素铬对实验性糖尿病大鼠糖、脂质代谢的影响。方法;对四氧嘧啶诱导的糖尿病大鼠经灌胃给予有机铬(吡啶甲酸铬)水溶液治疗84天后,用葡萄糖氧化酶法分别观察口服有机铬200μg/d及400μg/d的糖尿病大鼠血糖水平;用酶法测定甘油三酯和胆固醇水平。实验分为4组:1组为正常对照组;2组为铬400μg/d治疗组:3组为铬200μg/d治疗组:4组为糖尿病模型对照组。4组均自由进食。结果:有机铬具有明显的降低血糖、血清甘油三酯和血清胆固醇水平的作用(P<0.05～<0.001)。结论:铬能明显改善糖尿病大鼠的糖、脂代谢。     

Hp根治治疗对非酒精性脂肪性肝病患者血清细胞因子和血脂水平的影响

目的 研究幽门螺杆菌(Hp)根治治疗对Hp阳性的非酒精性脂肪性肝病(NAFLD)患者血清炎性因子和脂质代谢的影响。方法 2015年6月～2019年6月我院收治的168例Hp阳性的NAFLD患者,采用随机数字表法分为两组,每组84例。给予对照组多烯磷脂酰胆碱胶囊和二甲双胍联合治疗,观察组在对照组治疗的基础上行标准的Hp根治治疗。采用放射免疫法测定血清肿瘤坏死因子α(TNF-α)水平,采用比色法测定血清超敏C反应蛋白(hs-CRP)水平,采用ELISA法测定白介素6(IL-6)和IL-8水平。采用放射免疫法测定空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。结果 在根治治疗1个月后,观察组Hp根除率为94.0%,而对照组无Hp转阴病例(P＜0.05);治疗后,观察组血清TNF-α水平为(12.6±2.5)ng/L,显著低于对照组【(28.6±5.5)ng/L,P＜0.05】,血清hs-CRP水平为(7.5±1.4)mg/L,显著低于对照组【(14.6±2.6)mg/L,P＜0.05】,血清IL-6水平为(12.5±2.3)ng/L,显著低于对照组【(29.6±5.4)ng/L,P＜0.05】,和血清IL-8水平为(80.4±23.7)ng/L,显著低于对照组【(145.2±38.1)ng/L,P＜0.05】;观察组TC为(3.1±0.9)mmol/L,显著低于对照组【(4.8±0.7)mmol/L,P＜0.05】,TG为(1.5±0.8)mmol/L,显著低于对照组【(2.9±0.7)mmol/L,P＜0.05】,LDL-C为(0.9±0.4)mmol/L,显著低于对照组【(1.7±0.5)mmol/L,P＜0.05】,而HDL-C为(2.4±0.3)mmol/L,显著高于对照组【(1.8±0.4)mmol/L,P＜0.05】;观察组FINS为(16.0±5.2)μIU/ml,显著低于对照组【(19.0±6.4)μIU/ml,P＜0.05】,HOMA-IR为(3.9±2.4),显著低于对照组【(4.4±3.1),P＜0.05】。结论 根治Hp治疗对降低Hp阳性的NAFLD患者血清炎性因子水平、纠正糖脂代谢紊乱和改善肝功能具有重要的作用。     

脂质代谢相关microRNA概述

microRNA是基因表达过程的重要调控因子,其在细胞分化、增殖、凋亡及脂质代谢等多个方面都发挥着非常重要的作用,microRNA对脂质代谢的调节一直是近些年生物医学的研究热点。脂质代谢相关microRNA主要包括microRNA-33、microRNA-122、microRNA-370、microRNA-758、microRNA-27、microRNA-30c、microRNA-223、microRNA-144等,特别是microRNA-122和microRNA-33在调节体内胆固醇和脂肪酸平衡方面起主要作用。microRNA影响着细胞分化及脂质代谢等多种生物过程,其自身也受到转录因子、脂肪细胞因子和环境因素等的反馈调控,不同microRNA通过对mRNA的作用组成了复杂的调控网络。本文就microRNA调控脂质代谢的作用及方式进行综述。     

Liver X receptors bridge hepatic lipid metabolism and inflammation

Liver X receptors (LXRs) are members of the superfamily of metabolic nuclear receptors, which play central roles in the regulation of cholesterol absorption, efflux, transportation and excretion and many other processes correlating with lipid metabolism. LXRs can also regulate inflammation in vitro and in vivo. Accumulating evidence demonstrates that LXR are involved in the metabolism and inflammation in human diseases. Nonalcoholic fatty liver disease (NAFLD) is classically associated with lipid metabolic disorders and inflammatory responses, especially in the nonalcoholic steatohepatitis (NASH) phase. The effects of LXRs on cholesterol metabolism and inflammation make them attractive as a potential target for the treatment of NAFLD. Since the ability to synthesize triglycerides may be protective in obesity and fatty liver, the hepatic lipogenesis by LXRs should not rule out the possibility of the use of LXRs in NAFLD.     

Expression profiling suggests a regulatory role of gallbladder in lipid homeostasis

AIM:To examine expression profile of gallbladder using microarray and to investigate the role of gallbladder in lipid homeostasis. METHODS: 33P-labelled cDNA derived from total RNA of gallbladder tissue was hybridized to a cDNA array representing 17 000 cDNA clusters. Genes with intensities ≥2 and variation <0.33 between two samples were considered as positive signals with subtraction of background chosen from an area where no cDNA was spotted. The average gray level of two gallbladders was adopted to analyze its bioinformatics. Identified target genes were confirmed by touch-down polymerase chain reaction and sequencing. RESULTS: A total of 11 047 genes expressed in normal gallbladder, which was more than that predicted by another author, and the first 10 genes highly expressed (high gray level in hybridization image), e.g. ARPC5 (2 225.88±90.46), LOC55972 (2 220.32±446.51) and SLC20A2 (1 865.21±98.02), were related to the function of smooth muscle contraction and material transport. Meanwhile, 149 lipid-related genes were expressed in the gallbladder, 89 of which were first identified (with gray level in hybridization image), e.g. FASN (11.42±2.62), APOD (92.61±8.90) and CYP21A2 (246.11±42.36), and they were involved in each step of lipid metabolism pathway. In addition, 19 of those 149 genes were gallstone candidate susceptibility genes (with gray level in hybridization image), e.g. HMGCR (10.98±0.31), NPC1 (34.88±12.12) and NR1H4 (16.8±0.65), which were previously thought to be expressed in the liver and/or intestine tissue only. CONCLUSION: Gallbladder expresses 11 047 genes and takes part in lipid homeostasis.