脂联素与非酒精性脂肪肝肝纤维化及胰岛素抵抗的关系

目的：研究脂联素水平与非酒精性脂肪肝（NAFLD）患者肝纤维化指标及胰岛素抵抗指数（IRI）的关系。方法：采用ELISA法检测NAFLD患者和正常对照组的脂联素水平及Ⅲ型前胶原（PCⅢ）、透明质酸（HA）、Ⅳ型胶原（CⅣ）、层黏蛋白（LN）水平,采用稳态模式胰岛素抵抗指数（HOMA IRI）评估胰岛素抵抗。结果：NAFLD组脂联素水平显著低于对照组,胰岛素抵抗指数与肝纤维化指标显著高于对照组（P〈0.05）,IRI与PCⅢ、PCⅣ、HA和LN呈显著正相关（P〈0.05）,脂联素水平与WHR、BMI、FBG、Tg、FINS、HOMA-IRI、PCⅢ、PCⅣ、HA和LN呈显著负相关（P〈0.01或〈0.05）。结论：NAFLD患者血清脂联素水平降低,脂联素的表达在NAFLD患者肝纤维化与胰岛素抵抗进程中可能起重要作用。     

冠状动脉疾病患者血清APN水平变化

目的：观察在冠心病（CHD）和高血压时血清脂联素（APN）水平的变化,分析低APN血症在CHD发生发展中的可能机制。方法：采用ELISA检测血清APN含量,比较各组心血管疾病患者血清APN水平的变化。结果：①心肌梗死患者血清APN水平最低,明显低于心绞痛（P〈0.05）、高血压（P〈0.05）、动脉粥样硬化（P〈0.01）和其它疾病（P〈0.01）组;②心绞痛组明显低于其它疾病（P〈0.01）组,但与高血压、动脉粥样硬化组比较无显著性差异（P〉0.05）;③心肌梗死、心绞痛、高血压、动脉粥样硬化组患者血清APN水平均明显低于正常对照组,其它疾病组与正常对照组无明显差异（P〉0.05）。结论：CHD和高血压患者血清APN水平与其血管病变密切相关,检测患者血清APN水平有助于观察冠状动脉疾病的病情变化。     

肝硬化患者血清TPO水平与APN和HA水平相关性探讨

目的：探讨肝硬化患者血清血小板生成素（TPO）水平与脂联素（APN）和HA的相关性。方法：应用放射免疫分析和酶联法对63例肝硬化患者进行血清TPO、APN和HA检测,并与35名正常健康人作比较。结果：肝硬化患者血清TPO、APN水平均非常显著地低于正常人组（P〈0.01）,而HA水平则显著地高于正常人组（P〈0.01）,血清TPO水平与APN水平呈正相关（r=0.6284,P〈0.01）,与HA水平呈负相关（r=-0.4982,P〈0.01）。结论：肝硬化患者血清TPO、APN和HA水平与疾病的发生、发展密切相关,有重要的临床价值。     

原发性高血压肾病患者血清APN、TGF-β_1检测的临床意义

目的：探讨了原发性高血压肾病患者血清脂联素（APN）、TGF-β1水平的变化及意义。方法：应用ELISA在36例高血压肾病患者进行血清APN、TGF-β1检测,并与35名正常健康人作比较。结果：原发性高血压肾病患者TGF-β1水平非常显著地高于正常人组（P〈0.01）。血清APN水平则低于正常人组（P〈0.01）。两者之间呈明显负相关（r=-0.4588,P〈0.01）。结论：检测原发性高血压肾病患者血清APN和TGF-β1水平的变化对了解病情,探讨其发病机理,预防和指导用药均有重要的临床价值。     

急性颅脑损伤患者血浆NT和血清hs-CRP、APN检测的临床意义

目的：探讨了急性颅脑损伤患者治疗前后血浆神经降压素（NT）和血清hs-CRP、脂联素（APN）水平的变化及临床意义。方法：应用放射免疫分析、免疫比浊法和酶联法对36例急性颅脑损伤患者进行治疗前后血浆NT和血清hs-CRP、APN检测,并与35名正常健康人作比较。结果：急性颅脑损伤患者治疗前血浆NT和血清hs—CRP水平非常显著地高于正常人组（P〈0．01）,而血清APN水平又非常显著地低于正常人组（P〈0．01）。经综合治疗2周后则与正常人组比较无显著性差异（P〉0．05）,血清APN水平与NT、hs．CRP水平呈显著负相关（r=-0．6108、-0．5984,P〈0．01）结论：检测急性颅脑损伤患者血浆NT和血清hs—CRP、APN水平的变化对了解病情、观察疗效和预后判定均有一定的临床价值。     

120例ICP患者血清中CG、TBA与TSH水平变化分析

目的探讨妊娠期肝内胆汁淤积症（ICP）患者血清中甘胆酸（CG）、总胆汁酸（TBA）与促甲状腺激素（TSH）水平的变化及其临床意义。方法选取妊娠期肝内胆汁淤积症（ICP）患者120例为实验组,对照组为94例正常妊娠者,分别测定其甘胆酸（CG）、总胆汁酸（TBA）与促甲状腺激素（TSH）水平并进行比较。结果与正常妊娠组相比,ICP患者血清中CG、TBA及TSH水平均显著升高,差异有统计学意义（P〈0.05～0.01）。结论监测ICP患者血清中CG、TBA及TSH水平的变化对判断病情,指导临床具有重要价值。     

血浆Hcy和肝纤维化指标检测在NAFLD患者中的临床应用

目的：探讨血浆同型半胱氨酸（Hcy）和肝纤维化指标检测在非酒精脂肪性肝病（NAFLD）患者中的临床意义。方法：对符合临床诊断标准的257例非酒精脂肪肝患者进行Hcy、HA、PCⅢ、CⅣ、LN检测,并以同期体检健康者作为对照。结果：单纯性NAFLD患者Hcy、HA、PCⅢ结果高于对照组,差异有显著性（P〈0.05）,而CⅣ、LN结果虽高于对照组,但增高不明显,差异无显著性（P〉0.05）,非酒精性脂肪性肝炎（NASH）患者Hcy、HA、PCⅢ、CⅣ、LN结果明显高于对照组,差异有显著性（P〈0.01）或（P〈0.05）。NAFLD患者重度组与轻、中度组之间Hcy、HA、PCⅢ、CⅣ、LN差异均有显著性（P〈0.01）,中度脂肪肝与轻度脂肪肝之间Hcy、HA、PCⅢ、CⅣ、LN差异无显著性（P〉0.05）。结论：重度NAFLD患者存在不同程度的肝纤维化趋向,Hcy、HA、PCⅢ、CⅣ、LN结果是NAFLD筛查的实验室重要指标,可作为NAFLD病情监控和疗效评估的重要依据。     

肺间质纤维化患者血清MMP9和PⅢP检测的临床意义

目的：评价检测血清基质金属蛋白酶9（MMP9）和Ⅲ型前胶原肽（PⅢP）在肺间质纤维化中的应用价值。方法：用酶联免疫吸附试验（ELISA）检测血清中MMP9含量,用放射免疫分析（RIA）检测血清中PⅢP的含量。两项结果与正常对照组相比较。结果：肺间质纤维化组MMP9与PⅢP水平明显高于正常对照组,两项结果与正常对照组比较差异有显著性（P〈0.05或〈0.01）。结论：可作为了解肺间质纤维化进程及肺间质纤维化辅助诊断的指标。     

甘利欣联合苦参素治疗慢性乙型病毒性肝炎肝纤维化指标的变化

目的观察联合应用甘利欣和苦参素治疗慢性乙型病毒性肝炎患者血清肝纤维化指标的变化。方法选择39例慢性乙型病毒性肝炎中度患者,随机分成：治疗组19例,联合应用甘利欣和苦参素治疗;甘利欣组20例,给予甘利欣治疗。分别于治疗前后一周内检测血清肝纤维化指标HA、LN、ⅣP。结果两组治疗前血清HA、LN、ⅣP均明显高于正常对照组（P〈0.05）。两组患者治疗后的血清HA、LN、ⅣP水平较治疗前降低,治疗组血清HA、LN、ⅣP水平治疗前后存在统计学差异,且明显低于甘利欣组治疗后水平（P〈0.05）。结论苦参素和甘利欣合用较与单纯应用甘利欣治疗慢性乙型肝炎可明显改善肝纤维化指标,说明苦参素有较强的抗肝纤维化作用。     

COPD患者治疗前后血清IL-18、D-D和APN检测的临床意义

目的：探讨了COPD患者治疗前后血清IL-18、D．D和APN水平的变化及临床意义。方法：应用酶联法和生化法对40例COPD患者进行了治疗前后血清IL-18、D．D和APN检测,并与35名健康人作比较。结果：COPD患者在治疗前后血清IL-18、D-D和APN水平均非常显著地高于正常人组（P〈0．01）,经治疗2周后则与正常人组比较无显著性差异（P〉0．05）,且血清IL-18水平与D．D、APN水平呈显著正相关（r=0．5018、0．6134,P〈0．01）。结论：检测COPD患者血清IL-18、D-D和APN水平的变化对了解病情、观察疗效和预后判定均具有一定的临床意义。     

血清YKL-40对非酒精性脂肪肝肝纤维化的预测作用

目的探讨非酒精性脂肪肝患者血清中YKL-40水平及在肝纤维化程度评价中的价值。方法2017年7月至2019年7月于我院就诊的NAFLD患者142例,根据是否发生肝纤维化分为纤维化组(n=60)与非纤维化组(n=82),另纳入40例健康体检者作为健康对照组,采用放射免疫分析法测定血清中透明质酸(HA)、III型前胶原(PC III)、IV型胶原(CIV)及层粘连蛋白(LN)水平。采用双夹心抗体ELISA法检测血清YKL-40水平。结果三组研究对象年龄、性别、BMI指数等一般性资料差异无统计学意义(P>0.05);健康对照组、S0~S4期血清YKL-40水平随着肝纤维化分期的不断增加而不断升高(P<0.05)。血清YKL-40水平与NFS、FIB-4、APRI评分均呈显著正相关关系,具有统计学意义(P<0.05)。ROC分析结果表明,当Cutoff值为158 ng/mL时,YKL-40对NAFLD患者肝纤维化诊断价值最高,其AUC、灵敏度、特异性、PPV、NPV等均高于传统肝纤维化指标,差异具有统计学意义(P<0.05)。结论血清YKL-40在非酒精性脂肪肝患者中水平明显升高,对肝纤维化具有良好的预测价值。     

Concentrations of connective tissue growth factor in patients with nonalcoholic fatty liver disease: Association with liver fibrosis

Aim: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice. Methods: Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA. Results: Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P=0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1-2) 519.9 ± 375.2 and with advanced fibrosis (stage 3-4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t=5.6, P <0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages. Conclusion: Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis.     

利拉鲁肽对非酒精性脂肪肝大鼠脂联素及胰岛素抵抗的影响

 目的：观察利拉鲁肽（Lira）对非酒精性脂肪肝（NAFLD）大鼠血清和肝组织脂联素（ADP）及胰岛素抵抗的影响。方法：雄性SD大鼠30只,随机分为3组,分别予普通饮食（ND组）10只、高脂饮食（HFD组）10只和高脂饮食加利拉鲁肽腹腔注射（Lira组）10只。高脂饮食12周建立大鼠NAFLD模型,建模成功后Lira组予利拉鲁肽腹腔注射治疗4周。16周末处死各组大鼠,生物化学法检测丙氨酸氨基转移酶（ALT）、空腹血糖（FBG）、甘油三酯（TG）及总胆固醇（TC）,分光光度计测定游离脂肪酸（FFAs）,酶联免疫吸附法测定胰岛素和ADP。结果：与HFD组比较,Lira组大鼠体质量、肝指数、胰岛素抵抗指数、血清TG、TC、ALT、FBG及肝匀浆TG、TC、FFAs显著下降（均P<0.05）,血清及肝组织ADP明显升高（P＜0.05）,肝脏脂肪变性程度明显减少至恢复正常（P<0.05）,肝组织ADP含量与肝脏FFAs含量呈负相关。结论:利拉鲁肽改善胰岛素抵抗和肝脏脂肪变的可能机制之一与其升高血清及肝组织脂联素水平有关。     

非酒精性脂肪肝患者脂代谢紊乱与血清补体C3的相关性研究

目的:研究血清补体C3与非酒精性脂肪肝发病危险因素及非酒精性脂肪肝发生发展的相关性.进而了解C3在非酒精性脂肪肝患者血清中含量变化的意义.方法:40例健康对照组、40例单纯转氨酶升高组、40例非酒精性脂肪肝转氨酶正常组、40例非酒精性脂肪肝转氨酶升高组.按脂肪肝患者ALT是否升高分为转氨酶正常组和异常组.用酶联免疫吸附...     

Clinicopathological correlations in a series of adult patients with non‐alcoholic fatty liver disease

Possible correlations among clinical data, serum aminotransferase levels and histological features were assessed in a series of 37 adult patients with non‐alcoholic fatty liver disease (NAFLD), consisting of nine patients with fatty liver (FL) and 28 with non‐alcoholic steatohepatitis (NASH). In each liver biopsy, the NAFLD activity score (NAS) and the stage of fibrosis were determined. Additionally, the number of Kupffer cell aggregates (microgranulomas) per centimeter of biopsy length (MG/cm ratio) was assessed on immunohistochemical stains for CD68 antigen. Definite NASH (NAS ≥ 5) was strongly correlated with serum aspartate aminotransferase (AST) level (P= 0.003), stage of fibrosis (P= 0.003) and age (P= 0.014). On multivariate analysis, age >46 years and AST level above normal values were found to be independent clinical predictors of established NASH. The MG/cm ratio increased from control liver to FL to NASH (P < 0.001), and was correlated with the NAS (P= 0.003) and with the stage of fibrosis (P= 0.004), but not with the serum aminotransferase levels. In conclusion, persistent AST elevation in patients with suspected NAFLD should be an indication for liver biopsy, in order to determine the severity of necroinflammatory activity and the stage of fibrosis. Microgranuloma counting may represent a useful complementary marker of necroinflammatory activity in patients with NAFLD.     

非酒精性脂肪肝患者血清AFP水平及其应用价值

目的 检测非酒精性脂肪肝（NAFLD）患者血清AFP水平,并探讨其应用价值.方法 对97例患者进行评估,患者通过做腹部超声诊断确定为脂肪肝,并分成3个组.无脂肪肝患者作为对照组.所有患者和对照组进行体格检查、肝功能检测、稳态模型法评估胰岛素抵抗指数（HOMA-IR）检测.结果 体质指数、AST、ALT、血糖、HOMA-IR等在NAFLD患者中高于对照组.TG、总胆固醇、LDL-C、HDL-C水平在NAFLD中高于对照组.AFP水平在NAFLD中比对照组显著升高（5.43±2.65 IU/mL vs 2.33±0.99 IU/mL,P＜0.05）.三级NAFLD AFP水平显著高于一级NAFLD （6.69±2.36 IU/mLVS 3.56±1.60 IU/mL,P＜0.05）和二级NAFLD AFP水平（6.69±2.36 IU/mL VS 4.27±1.79 IU/mL,P＜0.05）.另外,二级NAFLD AFP水平显著高于一级NAFLD（P＜0.05）.ALT、AST与其无相关性.结论 NAFLD患者AFP水平高于非脂肪肝患者,AFP水平与脂肪病分级有关,NAFLD分级与血清AFP水平的相关性独立于其它因素.     

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease

Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Results: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t =2.226, P < 0.01). Conclusions: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.     

糖尿病非酒精性脂肪肝病大鼠肝组织胰岛素受体、瘦素受体 mRNA的表达

目的：观察2型糖尿病大鼠肝脏的病理变化,探讨肝组织胰岛素受体（insulin R）、瘦素受体（leptin R）mRNA表达在糖尿病性非酒精性脂肪肝病（NAFLD）发病机制中的作用。方法：SD大鼠随机分成2组：正常组与2型糖尿病组。2型糖尿病组在以高脂饮食4周后,加小剂量(30 mg/kg)链脲佐菌素（STZ）诱导2型糖尿病性非酒精性脂肪性肝病大鼠模型,继续给予高脂饮食12周。分别采用HE染色、苏丹Ⅲ染色、Masson染色光镜下观察肝脏组织的病理改变;透射电镜观察肝脏超微结构改变;生化法检测血糖、血甘油三酯（TG）、血总胆固醇（TC）、丙氨酸转氨酶（ALT）和天门冬氨酸转氨酶（AST）水平;放免法检测血清胰岛素水平;ELISA法检测血清瘦素水平;RT-PCR法检测肝组织磷酸烯醇式丙酮酸羧激酶（PEPCK）、葡萄糖-6-磷酸酶（G6Pase）、insulin R、leptin R mRNA表达水平。结果：糖尿病大鼠肝细胞明显脂肪变性、碎片状坏死伴炎细胞浸润及肝纤维化病变,电镜下主要表现为肝细胞核固缩,胞浆内含大量脂滴,狄氏间隙胶原纤维增生;血糖、血胰岛素、TG、ALT、AST水平明显升高（P<0.01）,TC水平升高(P<0.05）,血清瘦素水平明显下降（P<0.01）;肝组织insulin R、leptin R mRNA表达显著升高（P<0.01）,PEPCK、G6Pase mRNA表达无显著变化。结论：2型糖尿病时的胰岛素抵抗是NAFLD发生的根源,由于胰岛素抵抗而致的低血清瘦素水平、肝组织insulin R、leptin R 表达上调参与了NAFLD的发生。     

Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

Background/Aims

Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD.

Methods

A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day.

Results

The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001).

Conclusions

Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.