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酒精性肝硬化患者血清脂肪因子的临床意义分析

2017-02-23魏新亮魏思忱田树英孔郁

中国当代医药 2016年32期
关键词:脂联素胰岛素抵抗

魏新亮++魏思忱++田树英++孔郁++王卫卫++姜红玉

[摘要]目的 探討酒精性肝硬化患者血清脂肪因子的临床意义。方法 将2014年3月~2016年3月于河北省沧州市中心医院住院治疗的52例酒精性肝硬化患者作为肝硬化组,其中Child-Pugh分级A级17例,B级20例,C级15例;同时选择32名健康体检者作为对照组。检测并比较肝硬化组及不同Child-Pugh分级的肝硬化患者与对照组的血清网膜素、脂联素、内脏脂肪素及其他相关的临床生化参数;采用Spearman等级相关分析法及线性回归方程分析酒精性肝硬化患者血清脂肪因子与各生化指标的相关性。结果 肝硬化组患者血清网膜素、脂联素水平分别为(925.19±167.58)ng/L和(908.06±156.96)μg/L,明显高于对照组[(793.68±100.38)ng/L、(649.97±105.01)μg/L](P<0.05);肝硬化组患者内脏脂肪素水平为(18.61±3.75)μg/L,明显低于对照组[(23.39±6.15)μg/L](P<0.05);Child-Pugh分级A、B、C级肝硬化组患者间网膜素、脂联素、内脏脂肪素比较差异均无统计学意义(P>0.05),而随着Child-Pugh分级A、B、C级的逐渐增高,肝硬化组患者的HOMA-IR和IL-6水平也逐渐升高(P<0.05)。相关性分析结果显示,肝硬化组患者血清网膜素、脂联素、内脏脂肪素水平与胰岛素抵抗指数及胰岛素水平无明显相关性(P>0.05)。结论 肝硬化时网膜素、脂联素升高,内脏脂肪素下降,其可作为预测肝硬化的指标,但不能作为肝功能严重程度的评估指标。

[关键词]酒精性肝硬化;网膜素;脂联素;内脏脂肪素;Child-Pugh分级;胰岛素抵抗

[中图分类号] R575.5 [文献标识码] A [文章编号] 1674-4721(2016)11(a)-0018-04

Analysis of clinical significance of serum adipocyte factors of patients with alcoholic cirrhosis

WEI Xin-liang WEI Si-chen TIAN Shu-ying KONG Yu WANG Wei-wei JIANG Hong-yu

Deparment of Gastroenterlogy,the Central Hospital of Cangzhou City,Hebei Province,Cangzhou 061001,China

[Abstract]Objective To investigate the clinical significance of serum adipocyte factors in patients with alcoholic cirrhosis.Methods 52 patients with alcoholic cirrhosis from March 2014 to March 2016 in the Central Hospital of Cangzhou City were selected as liver cirrhosis group,among which 17 cases of class A of Child-Pugh grading,20 patients with class B,15 cases of grade C;and 32 healthy controls were selected as control group at the same time.Levels of serum omentin,adiponectin,visfatin and other related clinical and biochemical parameters were measured and compared between patients with liver cirrhosis,different Child-Pugh class of liver cirrhosis and control group.Spearman rank correlation analysis and equation of linear regression were used to analyzed the relationship between cirrhosis serum fat factors and the related biochemical indicators of patients with alcoholic liver.Results The levels of serum omentin and adiponectin in the liver cirrhosis group [(925.19±167.58) ng/L,(908.06±156.96) μg/L] were significantly higher than those of the control group [(793.68±100.38) ng/L,(649.97±105.01) μg/L] (P<0.05),level of serum visfatin in the liver cirrhosis group [(18.61±3.75) μg/L] was significantly lower than that of the control group [(23.39±6.15) μg/L] (P<0.05).The levels of serum omentin,adiponectin,visfatin of patients with different Child-Pugh grading of liver cirrhosis had no statistically significant difference (P>0.05).As the increase of Child-Pugh grading,the levels of group of insulin resistance index and IL-6 increased gradually in patients of the liver cirrhosis group (P<0.05). Correlation analysis results show that,there was no significant correlation between the levels of adiponectin,omentin,visfatin and insulin resistance index in the liver cirrhosis group.Conclusion The levels of serum adiponectin,omentin evidently increase and the level of serum visfatin decrease in patients with alcoholic cirrhosis,and can be a prediction index of liver cirrhosis,but which cant be use to evaluate the degree of liver cirrhosis.

[Key words]Alcoholic cirrhosis;Omentin;Adiponectin;Visfatin;Child-Pugh grading;Insulin resistance

长期以来,脂肪组织一直被认为是仅能供能量储备的终末分化器官。目前发现脂肪组织能够分泌多种脂肪因子,参与多种病理生理过程,脂肪因子在肝脏的脂肪变性、炎性坏死及纤维化、硬化方面起着重要作用。酒精性肝硬化是我国常见病,其本质为代谢性疾病。本研究观察了酒精性肝硬化患者血清网膜素、脂联素及内脏脂肪素(visfatin)水平的变化,并分析了其与肝功能、Child-Pugh分级、胰岛素抵抗指数(HOMA-IR)、白介素-6(IL-6)等因素间的关系,现报道如下。

1资料与方法

1.1一般资料

选择2014年3月~2016年3月于河北省沧州市中心医院(以下简称“我院”)消化内二科住院的酒精性肝硬化患者52例为研究对象(肝硬化组),所有患者均有明确的饮酒史、典型的CT表现以及门脉高压症的表现(如腹水、静脉曲张、脾功能亢进等)。其中男40例,女12例;Child-Pugh分级A级17例,B级20例,C级15例。排除合并肾功能损伤、心肺功能不全、代谢性疾病的患者。同时选择我院同期健康体检者32例作为对照组,其中男26例,女6例。

1.2指标测定

采集隔夜空腹8 h以上静脉血,用全自动生化仪检测肝功能、空腹血糖(FPG)、血脂、IL-6,检查凝血常规,经电化学发光法测定空腹胰岛素(FIns),收集血清经ELISA法检查网膜素、脂联素、visfatin。体重指数(BMI)=体重/身高2。采用HOMA-IR评价胰岛素抵抗,HOMA-IR=FBG×FIns/22.5。

1.3统计学方法

采用SPSS 13.0统计学软件进行数据分析,计量资料数据用均数±标准差(x±s)表示,多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验;采用Spearman等级相关分析法及线性回归方程分析酒精性肝硬化患者血清脂肪因子与各生化指标的相关性;以P<0.05为差异有统计学意义。

2结果

2.1肝硬化组与对照组的一般情况

肝硬化患者丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、凝血酶原时间、FIns、HOMA-IR、脂联素、网膜素、IL-6均高于对照组,差异均有统计学意义(P<0.05);肝硬化患者visfatin、白蛋白、三酰甘油均低于对照组,差异均有统计学意义(P<0.05);两组年龄、体重指数及FPG比较,差异均无统计学意义(P>0.05)(表1)。

2.2不同Child-Pugh分级肝硬化组患者及对照组各血清脂肪因子水平比较

肝硬化组Child-Pugh分级A、B、C级患者血清网膜素、脂联素、HOMA-IR及IL-6水平均较对照组明显升高,差异均有统计学意义(P<0.05),visfatin较对照组降低,差异有统计学意义(P<0.05)。而Child-Pugh分级A、B、C级肝硬化组患者间网膜素、脂联素、visfatin比较差异均无统计学意义(P>0.05),而随着Child-Pugh分级的逐渐增高,肝硬化组患者的HOMA-IR和IL-6水平也逐渐升高(P<0.05),C级患者明显高于A、B级患者,B级患者高于A级患者,差异均有统计学意义(P<0.05)(表2)。

2.3相关性分析

网膜素、脂联素、visfatin水平与HOMA-IR、FIns水平无明显相关性(P>0.05),与其他各项指标也无线性关系。

3讨论

网膜素是一种新的脂肪因子[1],可以提高胰岛素的敏感性,是一种有益的脂肪因子[2]。网膜素在非酒精性脂肪性肝病(non alcoholic fatty liver disease,NAFLD)患者血清中降低,原因考虑为NAFLD患者存在胰岛素抵抗,但网膜素水平与HOMA-IR無明显相关性[3-4]。肝硬化血清网膜素水平升高,与Child-Pugh分级及HOMA-IR无关,可能原因如下:①体重下降时HOMA-IR下降,网膜素水平升高,肝硬化时,随Child-Pugh分级加重,营养不良程度加重并导致消瘦,造成网膜素上升。②网膜脂肪组织网膜素mRNA水平与循环中雌二醇水平呈负相关[5],肝硬化患者体内雌激素水平升高,且随Child-Pugh分级加重而升高,可能造成网膜素水平下降,而未随Child-Pugh分级加重而升高。③肝硬化时腹膜及大网膜水肿[6];④肝硬化为一种炎症性疾病,网膜素在炎症性疾病时升高。

脂联素是由白色脂肪组织的成熟脂肪细胞特异性合成分泌的脂肪因子,是胰岛素增敏剂,在NAFLD中,APN水平下降[7]。本研究发现肝硬化患者虽然存在胰岛素抵抗,且随Child-Pugh分级加重而加重,但血清脂联素水平却较对照组升高,其原因可能为:①肝硬化时对脂联素的代谢清除减少[8];②肝细胞受损时脂联素mRNA及其蛋白表达增加[9];③慢性肝病胆汁淤积,胆汁排出减少[10]。

visfatin是由脂肪组织分泌的一种脂肪因子,可加重胰岛素抵抗。NAFLD患者visfatin上升,当发生非酒精性脂肪性肝炎时,visfatin水平下降,但较对照组升高[11]。visfatin基因在正常肝脏低表达,在重度肝纤维化中增加,同时在慢性肝损害患者中表达上调,在酒精性肝病中visfatin表达与炎症和纤维化程度密切相关。目前认为,visfatin可诱导IL-6的分泌[12],同时,IL-6也能调节visfatin mRNA在脂肪细胞中的表达[13],两者相互作用。本研究发现,肝硬化患者visfatin水平下降,原因主要为肝硬化时肝细胞visfatin mRNA表达下降,其水平变化可能如下:①肝硬化时多数存在胰岛素抵抗,并且随Child-Pugh分级加重而加重,胰岛素抵抗时visfatin水平上升,部分抵消了胰岛素抵抗;②肝硬化患者内脏脂肪减少;③肝硬化多存在低氧血症,而低氧、缺氧状态下机体内氧稳态的主要调节因子低氧诱导因子-1高表达,可直接上调visfatin的表达;④IL-6水平升高而上调visfatin水平;⑤visfatin在各种炎症时均升高,肝硬化本身为一种炎症性疾病[14];⑥肝硬化多数患者存在营养不良,而营养不良时visfatin水平上升,原因可能为visfatin可以促进体内烟酰胺的合成,而烟酰胺对营养状况的改善有一定作用[15]。

综上所述,本研究发现网膜素、脂联素在酒精性肝硬化时升高,visfatin下降,且与HOMA-IR无关,因此网膜素、脂联素及visfatin可作为肝硬化的预测指标,但不能作为肝功能严重程度的评价指标,如检测酒精性肝硬化患者血清网膜素、脂联素、visfatin水平,应从多方面考虑可能影响因素,综合分析,从而得出更合理的结论来指导临床。

[参考文献]

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[13]Kralisch S,Klein J,Lossner U,et al.Hormonal regulation of the novel adipo-cytokine visfatin in 3T3-L1 adipocytes[J].J Endoerinol,2005,185(3):1-8.

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[15]陳文宇,唐婷玉,杨琪,等.慢性阻塞性肺疾病患者血浆内脏脂肪因子水平变化及其与营养状况的关系[J].医学研究杂志,2013,42(4):60-63.

(收稿日期:2016-08-03 本文编辑:任 念)

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