王 曉，牟 君，楊澤松

·論著·

慢性丙型病毒性肝炎伴發(fā)焦慮抑郁癥患者血清載脂蛋白B的表達水平及意義研究

王 曉，牟 君，楊澤松

目的 探討慢性丙型病毒性肝炎(CHC)伴發(fā)焦慮抑郁癥患者血清載脂蛋白B(Apo B)表達水平及意義。方法 選取2010年1月—2014年6月于四川省達州市中心醫(yī)院住院的CHC患者100例為CHC組，另選取同時期本院體檢健康者100例為對照組。采用醫(yī)院焦慮和抑郁量表評估焦慮/抑郁癥程度,采用Olympus 3200型全自動生化分析儀檢測血清Apo B水平。比較對照組及不同焦慮或抑郁癥程度CHC患者血清Apo B水平的差異。結(jié)果 100例CHC患者中無焦慮組54例、輕度焦慮組20例、中重度焦慮組26例，無抑郁癥組74例、輕度抑郁癥組9例、中重度抑郁癥組17例。無焦慮組、輕度焦慮組、中重度焦慮組患者血清Apo B水平較對照組下降(P<0.05)；無焦慮組、輕度焦慮組、中重度焦慮組患者血清Apo B水平比較，差異無統(tǒng)計學(xué)意義(P>0.05)。無抑郁癥組、輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較對照組下降(P<0.05)；輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較無抑郁癥組下降(P<0.05)；中重度抑郁癥組患者血清Apo B水平較輕度抑郁癥組下降(P<0.05)。結(jié)論 CHC患者伴發(fā)焦慮抑郁癥與血清Apo B水平降低相關(guān)，血清Apo B水平下降與抑郁癥程度相關(guān)，而與焦慮程度無明顯相關(guān)關(guān)系。

肝炎，丙型,慢性；焦慮；抑郁癥；載脂蛋白B類

王曉，牟君，楊澤松.慢性丙型病毒性肝炎伴發(fā)焦慮抑郁癥患者血清載脂蛋白B的表達水平及意義研究[J].中國全科醫(yī)學(xué)，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.

近年來，我國丙型肝炎病毒(hepatitis C virus,HCV)感染的發(fā)病率及病死率呈逐年上升趨勢[1]。成人感染HCV后轉(zhuǎn)化為慢性肝炎的概率為75%～85%，還可導(dǎo)致肝硬化和肝癌的發(fā)生，嚴重危害生命健康[2]。情緒障礙是HCV感染常見的并發(fā)癥，據(jù)報道，慢性丙型病毒性肝炎(chronic hepatitis C，CHC)患者焦慮抑郁癥的患病率為28%[3]。長期以來，CHC被認為與膽固醇代謝障礙和血清膽固醇水平降低有關(guān)[4]。而血清膽固醇水平下降可增加自殺意念和行為[5]。國外有研究報道，載脂蛋白E(Apo E)缺乏可以導(dǎo)致CHC患者出現(xiàn)焦慮抑郁癥[6]。載脂蛋白B(Apo B)為低密度脂蛋白(LDL)的組分和細胞表面低密度脂蛋白受體(LDLR)的配體，在HCV感染過程中起重要作用。國內(nèi)外尚未見CHC患者Apo B水平與情緒障礙相關(guān)性的報道。本研究以臨床確診的CHC患者為研究對象，評定焦慮或抑郁癥評分，檢測其血清Apo B水平，初步探討CHC患者伴發(fā)焦慮抑郁癥與血清Apo B水平的相關(guān)性。

1 資料與方法

1.1 臨床資料 選取2010年1月—2014年6月于四川省達州市中心醫(yī)院住院的CHC患者100例為CHC組，其中男52例，女48例；年齡37～79歲，平均年齡(65.7±5.5)歲；CHC病程1～12年，平均CHC病程(7.9±3.2)年；無合并高血壓、糖尿病、冠心病、腦卒中、肺部疾病或其他器官疾病情況。入組標(biāo)準(zhǔn)：符合2004年中華醫(yī)學(xué)會肝臟病學(xué)分會公布的《丙型肝炎防治指南》的診斷標(biāo)準(zhǔn)[7]；排除正服用精神活性物質(zhì)者、大量吸煙或飲酒者、妊娠期婦女或哺乳期婦女或其他慢性肝臟疾病(甲型病毒性肝炎、乙型病毒性肝炎、戊型病毒性肝炎、藥物性肝炎、酒精性肝炎、自身免疫性肝炎等)及可引起脂代謝紊亂的其他疾病(如糖尿病、甲狀腺功能亢進)。另選取同時期本院體檢健康者100例為對照組，其中男50例，女50例；年齡42～75歲，平均年齡(63.5±4.4)歲。CHC組與對照組性別、年齡比較，差異無統(tǒng)計學(xué)意義(χ2=0.080,P=0.777；t=0.625，P=0.532)。受試者均簽署知情同意書。

1.2 焦慮抑郁癥評估 診斷CHC后，患者均完成醫(yī)院焦慮和抑郁量表(hospital anxiety and depression scale,HADS)[8]，總分21分。HADS焦慮癥狀(HADS-A)或HADS抑郁癥癥狀(HADS-D)<8分納入無焦慮組或無抑郁癥組；HADS-A或HADS-D 8～10分納入輕度焦慮組或輕度抑郁癥組；HADS-A或HADS-D≥11分納入中重度焦慮組或中重度抑郁癥組。

1.3 血清Apo B水平檢測 所有受試者空腹12 h后于次日清晨采集外周靜脈血2 ml，加入乙二胺四乙酸二鉀(EDTA-K2)抗凝試管，用于檢測血清Apo B水平。采用Olympus 3200型全自動生化分析儀檢測，方法為免疫比濁法，嚴格按照操作手冊進行。入選的CHC患者采血前均未進行臨床治療。

2 結(jié)果

2.1 焦慮抑郁癥情況 100例CHC患者中未伴發(fā)焦慮54例(54.0%)(無焦慮組)，伴發(fā)焦慮46例(46.0%)，其中輕度焦慮20例(20.0%)(輕度焦慮組)、中重度焦慮26例(26.0%)(中重度焦慮組)；未伴發(fā)抑郁癥74例(74.0%)(無抑郁癥組)，伴發(fā)抑郁癥26例(26.0%)，其中輕度抑郁癥9例(9.0%)(輕度抑郁癥組)、中重度抑郁癥17例(17.0%)(中重度抑郁癥組)。

2.2 對照組與不同焦慮程度CHC組患者血清Apo B水平比較 對照組與不同焦慮程度CHC組患者血清Apo B水平比較，差異有統(tǒng)計學(xué)意義(P<0.05)；其中無焦慮組、輕度焦慮組、中重度焦慮組患者血清Apo B水平較對照組下降，差異有統(tǒng)計學(xué)意義(P<0.05)；無焦慮組、輕度焦慮組、中重度焦慮組患者血清Apo B水平比較，差異無統(tǒng)計學(xué)意義(P>0.05，見表1)。

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

組別例數(shù)ApoB對照組100090±016無焦慮組54039±019a輕度焦慮組20034±015a中重度焦慮組26037±013aF值170545P值<0001

注：Apo B=載脂蛋白B；與對照組比較，aP<0.05

2.3 對照組與不同抑郁癥程度CHC組患者血清Apo B水平比較 對照組與不同抑郁癥程度CHC組患者血清Apo B水平比較，差異有統(tǒng)計學(xué)意義(P<0.05)；其中無抑郁癥組、輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較對照組下降，差異有統(tǒng)計學(xué)意義(P<0.05)；輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較無抑郁癥組下降，差異有統(tǒng)計學(xué)意義(P<0.05)；中重度抑郁癥組患者血清Apo B水平較輕度抑郁癥組下降，差異有統(tǒng)計學(xué)意義(P<0.05，見表2)。

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

組別例數(shù)ApoB對照組100090±016無抑郁癥組74042±012a輕度抑郁癥組9024±013ab中重度抑郁癥組17014±011abcF值267103P值<0001

注：與對照組比較，aP<0.05；與無抑郁癥組比較，bP<0.05；與輕度抑郁癥組比較，cP<0.05

3 討論

CHC患者大多數(shù)心理壓力較大，治療常達不到預(yù)期的效果，給患者身心帶來巨大的痛苦。有研究發(fā)現(xiàn)，影響CHC患者生活質(zhì)量的并不是疾病本身，而是焦慮抑郁癥[9]。本研究收集100例CHC患者，對該組患者行HADS評分，發(fā)現(xiàn)焦慮癥狀的檢出率為46.0%，低于前期文獻報道的79%[10]，抑郁癥的檢出率為26.0%，與前期文獻報道的28%相似[11]。伴發(fā)焦慮癥狀低于前期文獻的原因可能與患者年齡、性別的選取有一定關(guān)系，文獻報道發(fā)現(xiàn)，女性患者焦慮癥狀更為明顯[11]。

近年來研究發(fā)現(xiàn)，HCV感染與肝臟的血脂代謝紊亂關(guān)系密切，HCV通過結(jié)合人血清中的總膽固醇、Apo B、Apo E，形成脂病毒樣顆粒，再與肝細胞膜上LDLR結(jié)合，最終感染肝細胞[12]。本研究結(jié)果顯示，無焦慮組、輕度焦慮組、中重度焦慮組患者血清Apo B水平較對照組下降；無焦慮組、輕度焦慮組、中重度焦慮組患者之間血清Apo B水平無差異。無抑郁癥組、輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較對照組下降；輕度抑郁癥組、中重度抑郁癥組患者血清Apo B水平較無抑郁癥組下降；中重度抑郁癥組患者血清Apo B水平較輕度抑郁癥組下降。血清Apo B水平隨著抑郁癥程度的加重而下降。由此發(fā)現(xiàn)，CHC患者伴發(fā)焦慮抑郁癥與血清Apo B水平下降相關(guān)，血清Apo B水平下降與抑郁癥程度相關(guān)，而與焦慮程度無明顯相關(guān)關(guān)系。

CHC伴發(fā)抑郁癥可能與HCV直接感染或者感染后引起的腦代謝改變有關(guān)，如多巴胺能神經(jīng)遞質(zhì)紊亂、大腦免疫激活和小膠質(zhì)細胞激活[13]。有研究認為，CHC是一種與生理性和社會性相關(guān)的系統(tǒng)性慢性心身疾病，隨著對基礎(chǔ)慢性病的進一步認識，焦慮抑郁癥的發(fā)生率明顯增高[14]。焦慮抑郁癥與其他慢性病伴隨發(fā)生時，可使軀體疾病的癥狀復(fù)雜化，診斷治療難度增加，導(dǎo)致過度治療及軀體、社會功能缺陷[15]。既往較多研究證實，CHC患者較易伴發(fā)焦慮抑郁癥，部分患者在抗病毒治療前后均易出現(xiàn)焦慮抑郁癥[16]。

本研究不足之處在于樣本量較小，未能比較各型病毒性肝炎患者血清Apo B水平的差異，是否只有CHC伴發(fā)焦慮抑郁癥才會出現(xiàn)血清Apo B水平的改變尚需進一步研究。并應(yīng)進一步進行抗抑郁癥藥物治療，觀察治療前后血清Apo B水平的改變和血清Apo B水平的改變是否可以提示CHC伴發(fā)焦慮抑郁癥的治療效果，進一步闡明CHC伴發(fā)焦慮抑郁癥的發(fā)病機制，為臨床診斷、治療及預(yù)后提供新的思路。

作者貢獻：王曉進行試驗設(shè)計與實施、資料收集整理、撰寫論文、成文并對文章負責(zé)；王曉、楊澤松進行試驗實施、評估、資料收集；牟君進行質(zhì)量控制及審校。

本文無利益沖突。

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(本文編輯：陳素芳)

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

國家自然科學(xué)基金面上項目(81371310)；重慶市衛(wèi)生局面上項目(2012-2-033)

635000四川省達州市中心醫(yī)院消化內(nèi)科(王曉)；重慶醫(yī)科大學(xué)附屬第一醫(yī)院神經(jīng)內(nèi)科(牟君)，血液內(nèi)科(楊澤松)

王曉，635000四川省達州市中心醫(yī)院消化內(nèi)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)