HIF-1α对非酒精性脂肪性肝病小鼠肝组织的影响*

目的 探讨缺氧诱导因子1α(HIF-1α)在非酒精性脂肪性肝病(NAFLD)进展中的作用。方法 将30只雄性C57BL/6J小鼠随机分为对照组、高脂饮食模型组和蛋氨酸-胆碱缺乏饮食(MCD)模型组,每组10只,建立非酒精性脂肪性肝炎(NASH)模型,分别取肝组织行组织病理学检查,采用缺氧探针检测肝组织缺氧程度,采用Real-time PCR法检测肝组织HIF-1α mRNA水平,采用Western blot法检测肝组织HIF-1α蛋白表达。另取小鼠肝星状细胞JS-1细胞,分为对照组、腺病毒载体组和HIF-1α ShRNA腺病毒载体感染组,采用MTT法检测细胞活性,采用Real-time PCR法检测细胞1型胶原(COL1)和3型胶原(COL3)、TNF-α、IL-1β和TGF-β1 mRNA水平。结果 缺氧探针染色显示高脂饮食模型组和MCD模型组小鼠肝组织染色阳性率分别为85%和78%,显著高于对照组的7%(P<0.05);高脂饮食模型组和MCD模型组小鼠肝组织HIF-1α mRNA水平分别为对照组小鼠的2.1倍和1.6倍(P<0.05),HIF-1α蛋白表达水平也相应地增强;HIF-1α ShRNA腺病毒载体感染细胞活力仅为对照组的37%(P<0.05),细胞COL1、COL3、TNF-α、IL-1β、TGF-β1 mRNA水平也显著降低(P<0.05)。结论 HIF-1α能够促进小鼠NAFLD进展,抑制HIF-1α表达可能能延缓NAFLD进展,值得进一步研究。     

移植NAFLD患者和健康人粪菌对高脂饮食大鼠肠道菌群的影响*

目的 探讨粪菌移植干预对非酒精性脂肪性肝病(NAFLD)动物肠道菌群的影响。方法 将32 只大鼠随机分为ABCD四组,其中3组用混合抗生素抑菌1周后,予以高脂饮食建立NAFLD模型,再分别给予NAFLD患者粪菌或和正常人粪菌移植,检测肠粘膜组织16sDNA菌群。结果 模型组Rodentibacter菌群丰度较对照组升高,在NAFLD粪菌移植组升高更显著,而在正常人粪菌移植组则有所下降。结论 NAFLD粪菌群可能是肝脏脂肪变性的一个危险因素,而应用健康人粪菌移植可以改善高脂饮食大鼠脂肪肝病变。     

非酒精性脂肪肝自噬基因Beclin-1与核因子NF-κBp65表达研究

目的探讨自噬基因Beclin-1在高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠模型的表达及对NAFLD发病机制的影响。方法(1)选取24只成年雄性SD大鼠随机分为两组:NAFLD模型组(高脂饲料饲养)12只,正常组12只(普通饲料饲养)。连续饲养12周后处死两组大鼠,采取心脏取血法,检测血清生化学指标ALT、AST、TG、CHOL及低密度脂蛋白(LDL-C)。(2)将大鼠肝脏组织取出,取少许行病理切片,采用HE染色,光镜下观察肝脏组织病理变化,进一步评估肝脏脂肪变性程度及造模是否成功;免疫组化染色,确定NF-κBp65表达。(3)应用Western blot方法检测NAFLD造模成功后的大鼠肝组织中自噬基因(Beclin-1)蛋白的表达水平。结果(1)成功建立了大鼠NAFLD模型,血生化指标ALT、AST、CHOL、TG及LDL-C水平与对照组同期相比均明显升高(P=0.0422,0.0336,0.0405,0.0411,0.0433)。(2)Western blot图像结果显示,与对照组比较,模型组肝组织Beclin-1蛋白表达明显升高(P=0.0411)。(3)正常组大鼠肝小叶结构清晰完整,肝索呈放射状分布于中央静脉周围;模型组大鼠肝细胞内可见脂滴,NF-κBp65阳性,评分为44.01±0.22;免疫组化结果显示,NF-κB集中沉积在汇管区肝细胞胞浆,低倍镜视野下平均占细胞总数55.1 5±1.01%。结论自噬基因Beclin-1与NF-κBp65在NAFLD模型肝组织中表达水平升高并可能促进NAFLD发生发展过程。     

CDE饮食诱导慢性肝损伤小鼠肝组织YAP信号对肝祖细胞增殖的影响*

目的 探讨Yes相关蛋白(YAP)信号对胆碱缺乏/乙硫氨酸补充(CDE)饮食诱导慢性肝损伤模型小鼠肝组织胆管反应的影响以及体外对肝祖细胞增殖的影响。方法 采用CDE饮食喂养雄性野生型C57BL/6J小鼠3 w,采用Western blot和qPCR法检测肝组织YAP蛋白表达和基因水平;采用免疫组化法检测肝组织CK19表达,观察胆管反应程度;采用免疫荧光评估胆管反应细胞过程中YAP表达;采用两步灌注法分离原代肝祖细胞,以慢病毒感染肝祖细胞,将细胞分为YAP过表达(YAP-OE组)、过表达空载体(OE-control组)、YAP敲减(shYAP组)和敲减空载体(sh-control组),采用Western blot法检测肝组织YAP表达,采用CCK8和EdU实验评估YAP对肝祖细胞增殖能力的影响。结果 CDE造模组肝组织YAP蛋白表达比对照组增强,其YAP mRNA水平比对照组提高了2.45倍(P＜0.01);CDE造模组肝组织胆管反应程度和肝祖细胞YAP表达显著高于对照组;EdU检测发现在相同培养条件下,YAP-OE组EdU阳性细胞比例较OE-control组显著增加【分别为(0.41±0.05)和(0.25±0.06),P＜0.01】,CCK8检测提示在培养72 h时YAP-OE组细胞增殖活性比OE-control组提高了1.78倍(P＜0.01),而在相同培养条件下,EdU检测发现shYAP组EdU阳性细胞比例较sh-control组显著减少【分别为(0.25±0.04)和(0.13±0.02),P＜0.01】,在培养72h时CCK8检测提示shYAP组细胞增殖活性较sh-control组降低了1.92倍(P＜0.01)。结论 CDE饮食诱导小鼠慢性肝损伤导致肝组织胆管反应活跃的祖细胞YAP表达增强,YAP在体外能促进肝祖细胞增殖。     

非酒精性脂肪性肝病小鼠肝组织与脂质代谢相关基因FAS、ACC和SREBP-1水平分析*

目的 探讨非酒精性脂肪性肝病(NAFLD)小鼠肝组织脂质代谢相关基因水平变化。方法 采用高脂饲料喂养20小鼠,构建小鼠NAFLD动物模型,观察小鼠肝组织病理学变化,检测血清总胆固醇(TCH) 和甘油三酯(TG)含量,采用RT-PCR法检测小鼠肝组织胆固醇调节元件结合蛋白(SREBPs)、乙酰辅酶A羧化酶(ACC)和脂肪酸合成酶(fatty acid synthase, FAS)基因变化。结果 10只NAFLD模型小鼠肝细胞排列不整齐,肝细胞内出现大小不等的脂滴;NAFLD模型小鼠血清TG和TCH水平分别为(0.63±0.13)mmol/L和(7.23±0.7)mmol/L,显著高于10只对照组[(0.28±0.06)mmol/L和(2.78±0.6)mmol/L,P<0.001];在实验24 w末,NAFLD组小鼠肝组织FAS 和SREBP-1 mRNA水平分别为(3.9±1.1)和(1.8±0.7),对照组则分别为【(1.0±0.3)和(1.0±0.4),FAS: t = 6.231, P<0.001; SREBP-1: t =2.431, P =0.035】,差异显著,而NAFLD组小鼠肝组织ACC mRNA水平为(1.2±0.5),与对照组【(1.0±0.4), t=0.765, P=0.462】比,无显著差异。结论 NAFLD模型小鼠肝组织与脂质代谢相关基因显著上调,为进一步研究NAFLD的发生发展机制奠定了基础。     

葡萄糖神经酰胺葡萄糖基转移酶siRNA对7702肝细胞增殖的影响及机制研究*

目的 探讨糖鞘脂合成代谢在肝细胞增殖中的可能作用机制。方法 体外培养肝细胞株7702细胞,利用UDP-葡萄糖神经酰胺葡萄糖基转移酶（UGCG）siRNA转染肝细胞。采用MTT法检测细胞增殖,采用实时荧光定量PCR法检测Bcl-2、Bax和Caspase 3基因水平,采用Western blot法检测肝细胞Caspase 3蛋白表达情况。结果 UGCG siRNA干扰组细胞糖化神经酰胺合成酶基因水平比对照组明显下调（P<0.05）;干扰糖化神经酰胺合成酶基因表达后,转染组细胞Bcl-2 mRNA水平显著下降（P<0.05）,Bax mRNA水平显著升高,Caspase 3 mRNA及其蛋白表达水平均上调（P值均<0.05）。结论 糖化神经酰胺合成酶的缺乏引起的鞘脂代谢改变可能参与肝细胞的增殖的过程中,这可能与BCL2/BAX调节的细胞信号通路有关。     

柚皮素脂质体对非酒精性脂肪性肝病大鼠脂质代谢的影响及机制研究

目的 研究柚皮素脂质体对高糖高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠脂质代谢的影响及其机制。方法 将50只SD大鼠随机分为对照组、模型组、柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组。除对照组大鼠外,其余四组大鼠均采用高糖高脂饲料饲养建立模型,并分别给予生理盐水、柚皮素30 mg·kg^-1·d^-1、柚皮素脂质体20 mg·kg^-1·d^-1和柚皮素脂质体30 mg·kg^-1·d^-1腹腔注射,观察12 w。采用ELISA法检测血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)水平,采用Western blot法检测肝组织Nrf2蛋白表达,采用RT-PCR法检测肝组织Nrf2 mRNA水平。结果 模型组大鼠体质量、肝质量、血清TC、TG、ALT、AST、SOD、CAT和MDA水平分别为(547.6±19.8)g、(12.9±0.3)g、(1.2±0.2)mmol/L、(2.6±0.2)mmol/L、(69.8±5.3)U/L、(229.6±18.2)U/L、(29.9±6.4)U/L、(26.5±2.4)U/mg和(11.7±1.1)nmol/mL,而柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组大鼠上述大部分指标均有不同程度的下降(P＜0.05),仅SOD和CAT水平显著升高(P＜0.05);柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组大鼠肝组织Nrf2蛋白表达和Nrf2 mRNA水平均显著高于模型组。结论 柚皮素脂质体可有效降低NAFLD大鼠血脂水平,促进SOD和CAT生成,其机制可能与激活Nrf2有关。     

硫代乙酰胺诱导的急性肝损伤大鼠肝组织Norrin/Frizzled-4表达的变化*

目的 建立硫代乙酰胺（TAA）诱导的大鼠急性肝损伤模型,探讨Norrin/Frizzled-4在肝损伤间质重建中的作用。 方法 随机将32只SD大鼠分为正常对照组（N组）8只和TAA诱导组（M组）24只。建立TAA诱导的肝损伤大鼠模型。采用ELISA法检测血清CD105和血管内皮细胞生长因子（VEGF）水平,采用Western blot法检测原代肝星状细胞和肝组织Norrin/Frizzled-4信号通路中细胞外配体蛋白Norrin和细胞膜特异性受体蛋白Frizzled-4的表达。 结果 24只TAA诱导组大鼠死亡11只（45.8%）;病理学检查显示急性肝损伤大鼠模型建立成功;对照组血清CD105水平为（2.18±0.05） ng/mL,显著低于TAA处理1 w组的（2.36±0.07） ng/mL或2 w组的（2.42±0.03） ng/mL,差异均有显著性（P<0.05）;对照组血清VEGF为（61.48±0.39） pg/mL,显著低于模型组的（64.52±0.25） pg/mL,差异均有显著性（P<0.01）;原代肝星状细胞和正常肝组织不表达Norrin蛋白或Frizzled-4蛋白,或表达量很低,急性肝损伤大鼠肝组织Norrin/Frizzled-4表达显著高于正常对照组,差异均有显著性（P<0.01）。 结论 急性肝损伤大鼠肝组织Norrin/Frizzled-4蛋白表达上调,可能与急性肝损伤初期维持血管网络形态及肝间质重建有关。     

卡托普利对非酒精性脂肪性肝病大鼠肝细胞脂肪变性的影响

目的 研究卡托普利对非酒精性脂肪性肝病(NAFLD)大鼠肝细胞脂肪变性的影响。方法 随机将64只大鼠分为对照组16只(普通饲料喂养和生理盐水灌胃)、模型组16只(高脂饲料和生理盐水灌胃)、卡托普利处理组16只和罗格列酮处理组16只。给药6 w后取血清和肝组织,检测肝组织细胞色素氧化酶P4502E1(CYP2E1)mRNA水平及血清丙二醛(MDA)和谷胱甘肽(GSH)水平。结果 模型组肝细胞体积增大,见广泛性脂肪变性和细胞水肿,而卡托普利处理组大部分肝细胞排列正常,可见少量的脂肪变性,部分细胞水肿;卡托普利处理组血清AST、ALT、TC和TG水平分别为(94.1±15.6)U/L、(27.3±6.2)U/L、(1.4±0.2)mmol/L和(1.0±0.2)mmol/L,显著低于模型组【分别为(134.4±35.1)U/L、(35.2±7.1)U/L、(1.8±0.4)mmol/L和(1.4±0.2)mmol/L,P＜0.05】;卡托普利处理组肝湿重、肝指数和肝组织CYP2E1 mRNA水平分别为(11.7±2.1)g、(2.3±0.3)%和(1.8±0.2),显著低于模型组【分别为(14.3±2.0)g、(2.6±0.2)%和(2.3±0.1),P＜0.05】;卡托普利处理组血清MDA水平为(7.6±2.5)nmol/L,显著低于模型组【(12.1±2.6)nmol/L,P＜0.05】,而血清GSH水平为(41.0±17.5)mg/L,显著高于模型组【(22.2±10.2)mg/L,P＜0.05】。结论 卡托普利可有效减轻非酒精性脂肪性肝病大鼠肝细胞脂肪变性程度,可能与纠正脂代谢紊乱、恢复肝功能、增强抗氧化应激能力有关。     

Bcl-2、Bax蛋白表达在非酒精性脂肪性肝病中的作用

目的: 探讨凋亡调控蛋白Bcl-2、Bax表达在大鼠非酒精性脂肪性肝病(NAFLD)中的作用.方法: 采用高脂饮食建立大鼠NAFLD模型, 以正常饮食设立对照组. HE染色观察肝脏脂肪变、炎症活动和纤维化程度, 采用Western blot检测Bcl-2、Bax在肝脏组织中的表达.结果: 实验组大鼠4 wk可见轻度脂肪变, 8 wk呈单纯性脂肪肝改变, 至12 wk肝小叶内肝细胞弥漫性脂肪变, 伴大量炎性细胞浸润, 个别出现肝纤维化. Western blot结果显示, 实验组大鼠4、8、12 wk肝组织Bax蛋白表达显著高于对照组(0.61±0.03, 0.78±0.03, 1.02±0.03vs 0.51±0.03, 均P <0.01), Bcl-2蛋白随着造模时间的延长, 表达逐渐下降(0.39±0.01, 0.28±0.01, 0.15±0.01 vs 0.52±0.01, 均P <0.01),Bcl-2、Bax两者比率逐渐降低, 尤以12 wk降低明显.结论: 在NAFLD发生过程中, 细胞凋亡调节蛋白Bax表达上调, Bcl-2表达减少, 二者表达的相对比例发生异常. 这可能是NAFLD中肝细胞发生凋亡的重要原因之一.     

Adipose differentiation-related protein is a reliable lipid droplet marker in alcoholic fatty liver of rats

Background: Adipose differentiation‐related protein (ADRP) is a lipid droplet‐associated protein that coats cytoplasmic lipid droplets. The present study evaluated whether alcohol feeding enhances ADRP expression and whether ADRP is a lipid droplet marker in alcoholic fatty liver of rats. Because medium‐chain triglycerides (MCT) reduce alcoholic hepatosteatosis, their effects on ADRP were also evaluated. Methods: Fatty liver was induced in rats by the consumption of the Lieber‐DeCarli alcohol liquid diet with or without replacement of long‐chain triglycerides (LCT) by MCT (32% of calories). Immunohistochemical staining for ADRP was performed in formalin‐fixed, paraffin‐embedded liver sections. ADRP immunostaining was quantified by image analysis. Triacylglycerol was measured chemically. ADRP mRNA and protein were analyzed by real‐time polymerase chain reaction and western blot, respectively. Double staining technique was performed to distinguish ADRP from glycogen in hepatocytes. Results: Alcohol feeding for 21 days increased ADRP staining in the centrilobular and mid zonal regions of the liver lobules coincident with fat deposition in the liver. Replacing LCT in the alcohol diet with MCT diminished ADRP immunostaining in parallel with reduced steatosis. MCT also attenuated the up‐regulation of ADRP mRNA and protein after alcohol. In steatotic hepatocytes ADRP selectively stained the surface of macrovesicular and microvesicular lipid droplets. ADRP immunostaining quantitatively correlated with hepatic triacylglycerol levels, validating ADRP as a reliable lipid droplet marker. Compared with hematoxylin and eosin stains, ADRP was more sensitive in detecting microvesicular lipid droplets. ADRP immunostaining also distinguished lipid droplets from glycogen, as demonstrated by double staining for ADRP and glycogen. Conclusions: Alcohol induction of fatty liver enhances ADRP expression and MCT oppose the alcohol effects. ADRP is a reliable and sensitive marker for lipid droplets in alcoholic fatty liver. ADRP immunostaining permits quantification of fatty change in hepatocytes and can be used as an ancillary technique in assessing the efficacy of diets or drugs against hepatosteatosis.     

phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

AIM: To investigate the protein expression of phosphatase and tensin homolog(PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffinembedded liver sections of patients with non-alcoholic fatty liver disease(NAFLD)(n = 44) or alcoholic liver disease(ALD)(n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients' clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis(r = 0.3061, P = 0.0459) and the BMI(r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor(P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients(P 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.     

细胞凋亡在大鼠酒精和高脂饮食诱导的脂肪性肝病中的作用

目的探讨在实验性脂肪性肝病动物模型中肝细胞凋亡的作用。方法雄性Wistar大鼠46只，分为对照组、酒精组、高脂组和高脂加酒精组。制模成功后取血测血清ALT、AST、CHO、TG、FFA；PCR法和免疫组化法测定肝组织caspase-3的基因与蛋白表达；TUNEL法测定肝细胞凋亡指数；电镜下观察肝细胞凋亡情况。结果酒精组、高脂组、酒精加高脂组细胞凋亡指数分别为2．16±0．43、2．33±0．60和3．93±0．80，显著高于正常对照组（1．070．27，P〈0．05）；实验组caspase-3无论是基因还是蛋白表达均较对照组升高（P〈0．05），其中以酒精加高脂组增加最明显。析因分析显示，加用与不加用酒精或高脂饮食对caspase-3及其基因表达有显著性影响（P=0．00）；高脂饮食与酒精交互效应显著（P〈0．05）。结论酒精和高脂均能诱导肝细胞发生凋亡，同时酒精和高脂同时作用于肝脏加重肝细胞caspase-3的表达，两者具有协同损伤肝脏的作用。     

The preventive effect of liraglutide on the lipotoxic liver injury via increasing autophagy

Introduction and objectivesThe incidence of non-alcoholic fatty liver disease (NAFLD) is increasing. Previous studies indicated that Liraglutide, glucagon-like peptide-1 analogue, could regulate glucose homeostasis as a valuable treatment for Type 2 Diabetes. However, the precise effect of Liraglutide on NAFLD model in rats and the mechanism remains unknown. In this study, we investigated the molecular mechanism by which Liraglutide ameliorates hepatic steatosis in a high-fat diet (HFD)-induced rat model of NAFLD in vivo and in vitro.Materials and methodsNALFD rat models and hepatocyte steatosis in HepG2 cells were induced by HFD and palmitate fatty acid treatment, respectively. AMPK inhibitor, Compound C was added in HepG2 cells. Autophagy-related proteins LC3, Beclin1 and Atg7, and AMPK pathway-associated proteins were evaluated by Western blot and RT-PCR.ResultsLiraglutide enhanced autophagy as showed by the increased expression of the autophagy markers LC3, Beclin1 and Atg7 in HFD rats and HepG2 cells treated with palmitate fatty acid. In vitro, The AMPK inhibitor exhibited an inhibitory effect on Liraglutide-induced autophagy enhancement with the deceased expression of LC3, Beclin1 and Atg7. Additionally, Liraglutide treatment elevated AMPK levels and TSC1, decreased p-mTOR expression.ConclusionsLiraglutide could upregulate autophagy to decrease lipid over-accumulation via the AMPK/mTOR pathway.     

DKK3在非酒精性脂肪性肝病的作用研究

目的探讨Dickkopf-3(DKK3)在小鼠非酒精性脂肪性肝病(NAFLD)形成中的意义。方法采用高脂饮食喂养C57BL/6雄性小鼠来构建NAFLD模型,通过检测肝功能、糖代谢变化、肝脏组织中脂质含量及肝脏病理学变化评估NAFLD模型是否成功;并用Western印迹方法检测肝脏组织中DKK3蛋白变化情况。结果高脂饮食组小鼠NAFLD相关指标均较对照组升高,差异有统计学意义(P0.05)。高脂饮食组小鼠肝脏中DKK3蛋白表达量较对照组明显下降,定量分析比较差异有统计学意义(P0.05)。结论DKK3在NAFLD小鼠肝组织中表达明显下降,提示DKK3涉及NAFLD的发生发展过程,并可能发挥一定的作用。     

非酒精性脂肪性肝病大鼠肝X受体α基因表达变化及意义

目的研究NAFLD大鼠肝X受体α(LXRα)基因表达变化及意义。方法建立高脂饮食诱导NAFLD大鼠模型后,采用RT-RCR和Western blot法动态观察NAFLD大鼠肝组织中LXRα表达变化。结果4周时模型组大鼠血清游离脂肪酸含量达(0.33±0.03)mmol/L,对照组为(0.24±0.03)mmol/L,差异有统计学意义(P<0.05),随喂养时间延长逐渐升高,12周时模型组大鼠血清游离脂肪酸含量达(0.61±0.06)mmol/L,对照组为(0.25±0.01)mmol/L,差异有统计学意义(P<0.01)。血清ALT和AST含量在8周时模型组分别为75.8 U/L和138.9 U/L,对照组分别为54.8 U/L和81.4 U/L,差异有统计学意义(P<0.01),12周时模型组分别为102.3 U/L和179.1 U/L,对照组分别为54.3 U/L和79.2 U/L,差异有统计学意义(P<0.01)。2周时模型组大鼠肝组织中LXRα基因表达相对含量为0.62,对照组为0.33,差异有统计学意义(P<0.01),随着高脂饮食喂养时间的延长表达进一步增强,12周时模型组大鼠高达1.31,对照组为0.34,差异有统计学意义(P<0.01)。模型组大鼠肝组织中LXRα蛋白表达与基因表达趋势相同,与脂肪肝进展程度一致。结论LXRα基因表达变化与NAFLD的形成密切相关。