乙型病毒性肝炎患者血清sICAM-1水平及意義

1、    乙型病毒性肝炎患者血清sICAM-1水平及意義        摘要為探討乙型肝炎患者血清sICAM-1水平及其與肝損害的關(guān)系，用酶聯(lián)免疫法檢測7例正常人和74例HBV感染血清sICAM-1。結(jié)果：重型肝炎（重肝）早、中、晚期，及輕、中、重度慢性乙型肝炎（CHB）患者血清sICAM-1，均顯著高于正常人和無癥狀HBsAg攜帶者（AsC）；CHB患者肝功能越差、其血清sICAM-1水平越高，而重肝患者肝功能越差、其血清sICAM-1水平也越低。表明：從AsC至重肝早期，血

2、清sICAM-1水平隨著患者肝損害的加重而升高，能較好反映肝組織炎癥壞死程度，重肝患者血清sICAM-1水平隨著肝衰竭的加重而降低。關(guān)鍵詞細(xì)胞間粘附分子-1，病毒性肝炎中號 R512.6 SERUM LEVEL OF SOLUBLE INTERCELLULAR ADHESIONMOLECULE-1（sICAM-1） AND ITS CLINICAL SIGHNIFICANCE IN PATIENTS WITH VIRAL HEPATITIS BZhang Xuqing，Gu Changhai（Department of Infectious Diseases，Southwest Hospita

3、l，Third Military Medical University，Chongqing，400038）AbstractTo study the serum level of sICAM-1 and the relationships between sICAM-1 and liver injury of patients with hepatitis BSerum sICAM-1 was measured with ELISA from 7 healthy donors and 74 patients with HBV infectionResults demonstrated that

4、serum sICAM-1 was significantly increased in each stage of severe hepa-titis and in each type of chronic hepatitis，compared with healthy donors and AsCThe worse liver function there were，the higher levels of serum sICAM-1 were measured in CHB，and the lower levels of serum sICAM-1 were measured in SH

5、These results suggest that serum sICAM-1 be gradually increased following the aggravation of live injury of patients from AsC to the early stage of SH，and grossly reflect the degrees of liver inflammation and necrosisSerum sICAM-1 was decreased following the aggravation   of liver failure in SH

6、Key wordsViral Hepatitis，ICAM-1正常人的肝細(xì)胞缺乏細(xì)胞間粘附分子-1（ICAM-1）表達(dá)，而乙型肝炎患者的肝細(xì)胞膜ICAM-1表達(dá)明顯增強(qiáng)，其表達(dá)強(qiáng)度被認(rèn)為是反映肝組織炎癥損傷程度的較好指標(biāo)，但這需作免疫組化分析1?，F(xiàn)已知許多自身免疫性疾病患者血清sICAM-1水平有明顯增高，sICAM-1可以作為許多炎癥疾病病情觀察的重要免疫學(xué)指標(biāo)。本文探討乙型肝炎患者血清sICAM-1水平和變化規(guī)律，及其與患者病情、肝功能的關(guān)系。1材料與方法1.1研究對象正常人7例，男4例、女3例，平均年齡33.7歲。HBV感染者74例、均為我院1996年的住院病人，男66例、女8例，平均年

7、齡33.7歲；其中AsC 6例，輕度CHB9例、中度CHB9例、重度CHB14例，重肝（CSH）36例，其診斷均符合1995年病毒性肝炎防治方案的標(biāo)準(zhǔn)。1.2方法1.2.2血清sICAM-1用酶聯(lián)免疫法（ELISA）檢測，試劑盒由德國BoehRinger Mannheim公司提供。1.2.2血清甲、乙、丙、丁、戊5種肝炎病毒標(biāo)志均用ELISA法檢測。1.2.3血清丙氨酸轉(zhuǎn)氨酶（ALT）、門冬氨酸轉(zhuǎn)氨酶（AST）、TSB和凝血酶原時(shí)間（PT）均由我院檢驗(yàn)科檢測，由PT轉(zhuǎn)算出PTa。1.3統(tǒng)計(jì)學(xué)處理用t檢驗(yàn)和相關(guān)分析。2結(jié)果2.1乙型肝炎患者血清sICAM-1水平 見表1。重肝患者血清sICAM-

8、1水平顯著高于CHB患者，CHB患者血清sICAM-1水平顯著高于AsC和正常人。表 1乙型肝炎患者血清sICAM-1Tab 1Serum levels of sICAM-1 in patients with viral hepatits BGroupsnsCIAM-1（ngml）Healthy7217.9±30.3AsC6219.7±59.0CHB32833.1±490.6*CSH361176.9±230.8*?Compared with healthy donors，P0012.2HBV感染者血清sICAM-1變化規(guī)律見表2。在CHB，肝損害越重、其

9、血清sICAM-1水平則越高。重肝患者肝衰竭越重，其血清sICAM-1水平反而越低，但仍顯著高于輕、中度CHB和AsC。重肝早期患者血清sICAM-1水平顯著高于中、晚期患者，中期患者血清sICAM-1水平也顯著高于晚期患者。表 2HBV感染者血清sICAM-1變化Tab 2Changes of serum sICAM-1 in patients with HBV infectionGroupsnsCIAM-1（ngml）AsC62197±590*CHB（Mi）93679±1185*CHB（Mo）96139±1289*CHB（Se）1412734±404

10、4*SH（E）1014133±1676*SH（M）1212023±1631SH（L）149864±1378CHB（Mi）mild CHB，CHB（Mo）moderate CHB，CHB（Se）severe CHB，SH（E）the early stage of SH，SH（M）the middle stage of SH，SH（L）the late stage of SH*Compared with each other among 5 groups，P001Compared with each other among 3 groups，P005 2.3CHB患者

11、血清sICAM-1水平與肝功能的關(guān)系CHB患者血清sICAM-1水平越高，其PTa則越低，兩者間呈明顯負(fù)相關(guān)（r04022，P0.05）。CHB患者血清sICAM-1水平越高，其TSB也越高，兩者間呈顯示正相關(guān)（r06997，P0.01）。CHB患者血清sICAM-1水平與其血清AST之間呈顯示正相關(guān)（r03536，P0.05），而與血清ALT之間無明顯相關(guān)性（r01808，P0.05）。2.4重肝患者血清sICAM-1水平與肝功能的關(guān)系重肝患者血清sICAM-1水平越低，其PTa也越低，兩者間呈顯著正相關(guān)（r06047，P0.01）；血清sICAM-1水平越低，共TSB越高，兩者間呈顯著負(fù)相

12、關(guān)（r04483，P001）。血清sICAM-1水平與血清ALT無顯著相關(guān)（r00167，P005），也與血清AST無顯著相關(guān)（r00611，P005）。3討論CHB患者肝組織的肝細(xì)胞膜均有不同程度ICAM-1表達(dá)，其表達(dá)強(qiáng)度與肝組織炎癥壞死程度密切相關(guān)1，2。本研究發(fā)現(xiàn)，CHB患者血清sICAM-1水平明顯高于正常人和慢性無癥狀HBsAg攜帶者，重肝患者血清sICAM-1水平明顯高于CHB患者。說明乙型肝炎患者血清sICAM-1水平有不同程度升高，與其肝細(xì)胞膜有不同程度ICAM-1表達(dá)相一致。國外研究表明炎癥性肝病患者血清sICAM-1至少有三個(gè)來源：肝細(xì)胞合成釋放sICAM-1；由膜型IC

13、AM-1裂解脫落而來；細(xì)胞死亡后由肝細(xì)胞膜ICAM-1碎裂溶解入血3，4。重度CHB患者血清sICAM-1水平明顯高于中度CHB，中度CHB患者血清sICAM-1水平明顯高于輕度CHB。說明血清sICAM-1與肝細(xì)胞膜ICAM-1表達(dá)水平一樣，可作為反映CHB患者肝組織炎癥和肝損害程度的指標(biāo)。5。本研究顯示CHB患者血清sICAM-1水平越高，其血清總膽紅素也就越高、凝血酶原活動度則越低，說明血清sICAM-1水平與肝功能一致性較好、能較好反映CHB患者的肝功能損害程度。重肝患者肝衰竭越重，肝組織壞死也越明顯，殘存肝細(xì)胞很少，肝細(xì)胞合成釋放sICAM-1和凝血酶原也減少，處理膽紅素的能力也降低

14、，這就是重肝患者血清sICAM-1水平越低，其PTa也越低、TSB越高、肝衰竭越嚴(yán)重的原因之一；另外，重肝患者肝組織殘存肝細(xì)胞較少，肝細(xì)胞膜ICAM-1表達(dá)的絕對量也就較少，因此由肝細(xì)胞膜ICAM-1脫落而來的ICAM-1也就減少。乙型肝炎患者肝組織中浸潤的細(xì)胞毒性T細(xì)胞（CTL）表面有淋巴細(xì)胞功能相關(guān)抗原-1（LFA-1）表達(dá)，CTL能借助LFA-1與ICAM-1陽性HBV感染肝細(xì)胞粘附，攻擊破壞肝細(xì)胞6。血清中的sICAM-1能封閉CTL表面的LFA-1，競爭抑制CTL攻擊破壞靶細(xì)胞7。本研究顯示，從無癥狀HBsAg攜帶者至重型肝炎早期，血清sICAM-1水平均隨著肝損害的加重而升高；而在

15、重型肝炎，血清sICAM-1水平反而隨著肝損害的加重而降低，但仍顯著高于中、輕度慢性肝炎。一方面說明血清sICAM-1水平升高是肝組織炎癥壞死的結(jié)果，另一方面也顯示重型肝炎患者血清sICAM-1水平降低對其病情是不利的。作者簡介第一作者：男，33歲，博士，講師，主治醫(yī)師作者單位： 第三軍醫(yī)大學(xué)西南醫(yī)院傳染科，重慶400038參考文獻(xiàn)1Volpes R，Van Den Oord JJ，Desmet VJHepatic expression of intercellular adhesion molecule-1（ICAM-1） in viral hepatitis BHepatology，199

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