王 晓，牟 君，杨泽松

·论著·

慢性丙型病毒性肝炎伴发焦虑抑郁症患者血清载脂蛋白B的表达水平及意义研究

王 晓，牟 君，杨泽松

目的 探讨慢性丙型病毒性肝炎(CHC)伴发焦虑抑郁症患者血清载脂蛋白B(Apo B)表达水平及意义。方法 选取2010年1月—2014年6月于四川省达州市中心医院住院的CHC患者100例为CHC组，另选取同时期本院体检健康者100例为对照组。采用医院焦虑和抑郁量表评估焦虑/抑郁症程度,采用Olympus 3200型全自动生化分析仪检测血清Apo B水平。比较对照组及不同焦虑或抑郁症程度CHC患者血清Apo B水平的差异。结果 100例CHC患者中无焦虑组54例、轻度焦虑组20例、中重度焦虑组26例，无抑郁症组74例、轻度抑郁症组9例、中重度抑郁症组17例。无焦虑组、轻度焦虑组、中重度焦虑组患者血清Apo B水平较对照组下降(P<0.05)；无焦虑组、轻度焦虑组、中重度焦虑组患者血清Apo B水平比较，差异无统计学意义(P>0.05)。无抑郁症组、轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较对照组下降(P<0.05)；轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较无抑郁症组下降(P<0.05)；中重度抑郁症组患者血清Apo B水平较轻度抑郁症组下降(P<0.05)。结论 CHC患者伴发焦虑抑郁症与血清Apo B水平降低相关，血清Apo B水平下降与抑郁症程度相关，而与焦虑程度无明显相关关系。

肝炎，丙型,慢性；焦虑；抑郁症；载脂蛋白B类

王晓，牟君，杨泽松.慢性丙型病毒性肝炎伴发焦虑抑郁症患者血清载脂蛋白B的表达水平及意义研究[J].中国全科医学，2016，19(9)：1021-1023，1031.[www.chinagp.net]

Wang X,Mu J,Yang ZS.Expression and value of serum apolipoprotein B in patients with chronic hepatitis C accompanied by anxiety and depressive disorder[J].Chinese General Practice，2016，19(9)：1021-1023，1031.

近年来，我国丙型肝炎病毒(hepatitis C virus,HCV)感染的发病率及病死率呈逐年上升趋势[1]。成人感染HCV后转化为慢性肝炎的概率为75%～85%，还可导致肝硬化和肝癌的发生，严重危害生命健康[2]。情绪障碍是HCV感染常见的并发症，据报道，慢性丙型病毒性肝炎(chronic hepatitis C，CHC)患者焦虑抑郁症的患病率为28%[3]。长期以来，CHC被认为与胆固醇代谢障碍和血清胆固醇水平降低有关[4]。而血清胆固醇水平下降可增加自杀意念和行为[5]。国外有研究报道，载脂蛋白E(Apo E)缺乏可以导致CHC患者出现焦虑抑郁症[6]。载脂蛋白B(Apo B)为低密度脂蛋白(LDL)的组分和细胞表面低密度脂蛋白受体(LDLR)的配体，在HCV感染过程中起重要作用。国内外尚未见CHC患者Apo B水平与情绪障碍相关性的报道。本研究以临床确诊的CHC患者为研究对象，评定焦虑或抑郁症评分，检测其血清Apo B水平，初步探讨CHC患者伴发焦虑抑郁症与血清Apo B水平的相关性。

1 资料与方法

1.1 临床资料 选取2010年1月—2014年6月于四川省达州市中心医院住院的CHC患者100例为CHC组，其中男52例，女48例；年龄37～79岁，平均年龄(65.7±5.5)岁；CHC病程1～12年，平均CHC病程(7.9±3.2)年；无合并高血压、糖尿病、冠心病、脑卒中、肺部疾病或其他器官疾病情况。入组标准：符合2004年中华医学会肝脏病学分会公布的《丙型肝炎防治指南》的诊断标准[7]；排除正服用精神活性物质者、大量吸烟或饮酒者、妊娠期妇女或哺乳期妇女或其他慢性肝脏疾病(甲型病毒性肝炎、乙型病毒性肝炎、戊型病毒性肝炎、药物性肝炎、酒精性肝炎、自身免疫性肝炎等)及可引起脂代谢紊乱的其他疾病(如糖尿病、甲状腺功能亢进)。另选取同时期本院体检健康者100例为对照组，其中男50例，女50例；年龄42～75岁，平均年龄(63.5±4.4)岁。CHC组与对照组性别、年龄比较，差异无统计学意义(χ2=0.080,P=0.777；t=0.625，P=0.532)。受试者均签署知情同意书。

1.2 焦虑抑郁症评估 诊断CHC后，患者均完成医院焦虑和抑郁量表(hospital anxiety and depression scale,HADS)[8]，总分21分。HADS焦虑症状(HADS-A)或HADS抑郁症症状(HADS-D)<8分纳入无焦虑组或无抑郁症组；HADS-A或HADS-D 8～10分纳入轻度焦虑组或轻度抑郁症组；HADS-A或HADS-D≥11分纳入中重度焦虑组或中重度抑郁症组。

1.3 血清Apo B水平检测 所有受试者空腹12 h后于次日清晨采集外周静脉血2 ml，加入乙二胺四乙酸二钾(EDTA-K2)抗凝试管，用于检测血清Apo B水平。采用Olympus 3200型全自动生化分析仪检测，方法为免疫比浊法，严格按照操作手册进行。入选的CHC患者采血前均未进行临床治疗。

2 结果

2.1 焦虑抑郁症情况 100例CHC患者中未伴发焦虑54例(54.0%)(无焦虑组)，伴发焦虑46例(46.0%)，其中轻度焦虑20例(20.0%)(轻度焦虑组)、中重度焦虑26例(26.0%)(中重度焦虑组)；未伴发抑郁症74例(74.0%)(无抑郁症组)，伴发抑郁症26例(26.0%)，其中轻度抑郁症9例(9.0%)(轻度抑郁症组)、中重度抑郁症17例(17.0%)(中重度抑郁症组)。

2.2 对照组与不同焦虑程度CHC组患者血清Apo B水平比较 对照组与不同焦虑程度CHC组患者血清Apo B水平比较，差异有统计学意义(P<0.05)；其中无焦虑组、轻度焦虑组、中重度焦虑组患者血清Apo B水平较对照组下降，差异有统计学意义(P<0.05)；无焦虑组、轻度焦虑组、中重度焦虑组患者血清Apo B水平比较，差异无统计学意义(P>0.05，见表1)。

Table 1 Comparison of serum Apo B level among control group and CHC subgroups with different anxiety degrees

组别例数ApoB对照组100090±016无焦虑组54039±019a轻度焦虑组20034±015a中重度焦虑组26037±013aF值170545P值<0001

注：Apo B=载脂蛋白B；与对照组比较，aP<0.05

2.3 对照组与不同抑郁症程度CHC组患者血清Apo B水平比较 对照组与不同抑郁症程度CHC组患者血清Apo B水平比较，差异有统计学意义(P<0.05)；其中无抑郁症组、轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较对照组下降，差异有统计学意义(P<0.05)；轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较无抑郁症组下降，差异有统计学意义(P<0.05)；中重度抑郁症组患者血清Apo B水平较轻度抑郁症组下降，差异有统计学意义(P<0.05，见表2)。

Table 2 Comparison of serum Apo B level among control group and CHC subgroups with different depression degrees

组别例数ApoB对照组100090±016无抑郁症组74042±012a轻度抑郁症组9024±013ab中重度抑郁症组17014±011abcF值267103P值<0001

注：与对照组比较，aP<0.05；与无抑郁症组比较，bP<0.05；与轻度抑郁症组比较，cP<0.05

3 讨论

CHC患者大多数心理压力较大，治疗常达不到预期的效果，给患者身心带来巨大的痛苦。有研究发现，影响CHC患者生活质量的并不是疾病本身，而是焦虑抑郁症[9]。本研究收集100例CHC患者，对该组患者行HADS评分，发现焦虑症状的检出率为46.0%，低于前期文献报道的79%[10]，抑郁症的检出率为26.0%，与前期文献报道的28%相似[11]。伴发焦虑症状低于前期文献的原因可能与患者年龄、性别的选取有一定关系，文献报道发现，女性患者焦虑症状更为明显[11]。

近年来研究发现，HCV感染与肝脏的血脂代谢紊乱关系密切，HCV通过结合人血清中的总胆固醇、Apo B、Apo E，形成脂病毒样颗粒，再与肝细胞膜上LDLR结合，最终感染肝细胞[12]。本研究结果显示，无焦虑组、轻度焦虑组、中重度焦虑组患者血清Apo B水平较对照组下降；无焦虑组、轻度焦虑组、中重度焦虑组患者之间血清Apo B水平无差异。无抑郁症组、轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较对照组下降；轻度抑郁症组、中重度抑郁症组患者血清Apo B水平较无抑郁症组下降；中重度抑郁症组患者血清Apo B水平较轻度抑郁症组下降。血清Apo B水平随着抑郁症程度的加重而下降。由此发现，CHC患者伴发焦虑抑郁症与血清Apo B水平下降相关，血清Apo B水平下降与抑郁症程度相关，而与焦虑程度无明显相关关系。

CHC伴发抑郁症可能与HCV直接感染或者感染后引起的脑代谢改变有关，如多巴胺能神经递质紊乱、大脑免疫激活和小胶质细胞激活[13]。有研究认为，CHC是一种与生理性和社会性相关的系统性慢性心身疾病，随着对基础慢性病的进一步认识，焦虑抑郁症的发生率明显增高[14]。焦虑抑郁症与其他慢性病伴随发生时，可使躯体疾病的症状复杂化，诊断治疗难度增加，导致过度治疗及躯体、社会功能缺陷[15]。既往较多研究证实，CHC患者较易伴发焦虑抑郁症，部分患者在抗病毒治疗前后均易出现焦虑抑郁症[16]。

本研究不足之处在于样本量较小，未能比较各型病毒性肝炎患者血清Apo B水平的差异，是否只有CHC伴发焦虑抑郁症才会出现血清Apo B水平的改变尚需进一步研究。并应进一步进行抗抑郁症药物治疗，观察治疗前后血清Apo B水平的改变和血清Apo B水平的改变是否可以提示CHC伴发焦虑抑郁症的治疗效果，进一步阐明CHC伴发焦虑抑郁症的发病机制，为临床诊断、治疗及预后提供新的思路。

作者贡献：王晓进行试验设计与实施、资料收集整理、撰写论文、成文并对文章负责；王晓、杨泽松进行试验实施、评估、资料收集；牟君进行质量控制及审校。

本文无利益冲突。

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(本文编辑：陈素芳)

Expression and Value of Serum Apolipoprotein B in Patients With Chronic Hepatitis C Accompanied by Anxiety and Depressive Disorder

WANGXiao,MUJun,YANGZe-song.DepartmentofGastroenterology,DazhouCentralHospital，Dazhou635000，China

Objective To investigate the apolipoprotein B(Apo B) level and its significance of patients with chronic hepatitis C(CHC)accompanied by anxiety or depressive disorder.Methods A total of 100 CHC patients who were hospitalized in Dazhou Central Hospital of Sichuang Province from January 2010 to June 2014 were enrolled in CHC group and 100 healthy people determined by physical examination in the same hospital and the same period were enrolled as control group.The degrees of anxiety and depressive disorder were assessed by hospital anxiety and depression scale,and Apo B level was detected by fully automatic biochemical analyzer of Olympus 3200 type.Apo B level was compared among control group and CHC subgroups with different degrees of anxiety or depressive disorder.Results Among the 100 CHC patients,non anxiety group had 54 patients,mild anxiety group had 20 patients and moderately severe anxiety group had 26 patients;non depressive disorder group had 74 patients,mild depressive disorder group had 9 patients and moderately severe depressive disorder group had 17 patients.The serum Apo B levels of non anxiety group,mild anxiety group and moderately severe anxiety group were lower than those of control group(P<0.05);the differences in serum Apo B levels among non anxiety group,mild anxiety group and moderately severe anxiety group were not significant(P>0.05).The serum Apo B levels of non depressive disorder group,mild depressive disorder group and moderately severe depressive disorder group were lower than those of control group(P<0.05);the serum Apo B levels of mild depressive disorder group and moderately severe depressive disorder group were lower than those of non depressive disorder group(P<0.05);the serum Apo B level of moderately severe depressive disorder group was lower than that of mild depressive disorder group(P<0.05).Conclusion Anxiety and depressive disorder in CHC patients is related to the decrease of serum Apo B level and the decrease of serum Apo B level is related to the degree of depressive disorder but is not related to the degree of anxiety.

Hepatitis C,chronic；Anxiety；Depressive disorder；Apolipoproteins B

国家自然科学基金面上项目(81371310)；重庆市卫生局面上项目(2012-2-033)

635000四川省达州市中心医院消化内科(王晓)；重庆医科大学附属第一医院神经内科(牟君)，血液内科(杨泽松)

王晓，635000四川省达州市中心医院消化内科；E-mail:594574584@qq.com

R 512.63

A

10.3969/j.issn.1007-9572.2016.09.007

2015-06-24；

2016-01-19)