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乙型病毒性肝炎患者血清sICAM-1水平及意义
http://www.100md.com 《免疫学杂志》1999年第2期
     作者:张绪清 顾长海w'(y/1, 百拇医药

    单位:第三军医大学西南医院传染科,重庆400038w'(y/1, 百拇医药

    关键词:细胞间粘附分子-1,病毒性肝炎w'(y/1, 百拇医药

    免疫学杂志990214摘 要 为探讨乙型肝炎患者血清sICAM-1水平及其与肝损害的关系,用酶联免疫法检测7例正常人和74例HBV感染血清sICAM-1。结果:重型肝炎(重肝)早、中、晚期,及轻、中、重度慢性乙型肝炎(CHB)患者血清sICAM-1,均显著高于正常人和无症状HBsAg携带者(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:从AsC至重肝早期,血清sICAM-1水平随着患者肝损害的加重而升高,能较好反映肝组织炎症坏死程度,重肝患者血清sICAM-1水平随着肝衰竭的加重而降低。w'(y/1, 百拇医药

    中图号 R512.6w'(y/1, 百拇医药

    SERUM LEVEL OF SOLUBLE INTERCELLULAR ADHESIONw'(y/1, 百拇医药

    MOLECULE-1(sICAM-1) AND ITS CLINICALw'(y/1, 百拇医药

    SIGHNIFICANCE IN PATIENTS WITH VIRAL HEPATITIS Bw'(y/1, 百拇医药

    Zhang Xuqing,Gu Changhaiw'(y/1, 百拇医药

    (Department of Infectious Diseases,Southwest Hospital,Thirdw'(y/1, 百拇医药

    Military Medical University,Chongqing,400038)w'(y/1, 百拇医药

    Abstract To study the serum level of sICAM-1 and the relationships between sICAM-1 and liver injury of patients with hepatitis B.Serum sICAM-1 was measured with ELISA from 7 healthy donors and 74 patients with HBV infection.Results demonstrated that 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 AsC.The 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.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 necrosis.Serum sICAM-1 was decreased following the aggravation of liver failure in SH.

    Key words Viral Hepatitis,ICAM-1a&7n, 百拇医药

    正常人的肝细胞缺乏细胞间粘附分子-1(ICAM-1)表达,而乙型肝炎患者的肝细胞膜ICAM-1表达明显增强,其表达强度被认为是反映肝组织炎症损伤程度的较好指标,但这需作免疫组化分析[1]。现已知许多自身免疫性疾病患者血清sICAM-1水平有明显增高,sICAM-1可以作为许多炎症疾病病情观察的重要免疫学指标。本文探讨乙型肝炎患者血清sICAM-1水平和变化规律,及其与患者病情、肝功能的关系。a&7n, 百拇医药

    1 材料与方法a&7n, 百拇医药

    1.1 研究对象 正常人7例,男4例、女3例,平均年龄33.7岁。HBV感染者74例、均为我院1996年的住院病人,男66例、女8例,平均年龄33.7岁;其中AsC 6例,轻度CHB9例、中度CHB9例、重度CHB14例,重肝(CSH)36例,其诊断均符合1995年病毒性肝炎防治方案的标准a&7n, 百拇医药

    1.2 方法a&7n, 百拇医药

    1.2.2 血清sICAM-1用酶联免疫法(ELISA)检测,试剂盒由德国BoehRinger Mannheim公司提供。a&7n, 百拇医药

    1.2.2 血清甲、乙、丙、丁、戊5种肝炎病毒标志均用ELISA法检测。a&7n, 百拇医药

    1.2.3 血清丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)、TSB和凝血酶原时间(PT)均由我院检验科检测,由PT转算出PTa。a&7n, 百拇医药

    1.3 统计学处理 用t检验和相关分析。a&7n, 百拇医药

    2 结果a&7n, 百拇医药

    2.1 乙型肝炎患者血清sICAM-1水平 见表1。重肝患者血清sICAM-1水平显著高于CHB患者,CHB患者血清sICAM-1水平显著高于AsC和正常人。a&7n, 百拇医药

    表 1 乙型肝炎患者血清sICAM-1a&7n, 百拇医药

    Tab 1 Serum levels of sICAM-1 in patients with viral hepatits B Groups

    nmq{&$, 百拇医药

    sCIAM-1(ng/ml)mq{&$, 百拇医药

    Healthymq{&$, 百拇医药

    7mq{&$, 百拇医药

    217.9±30.3mq{&$, 百拇医药

    AsCmq{&$, 百拇医药

    6mq{&$, 百拇医药

    219.7±59.0mq{&$, 百拇医药

    CHBmq{&$, 百拇医药

    32mq{&$, 百拇医药

    833.1±490.6*mq{&$, 百拇医药

    CSHmq{&$, 百拇医药

    36mq{&$, 百拇医药

    1176.9±230.8*mq{&$, 百拇医药

    *Compared with healthy donors,P<0.01mq{&$, 百拇医药

    2.2 HBV感染者血清sICAM-1变化规律 见表2。在CHB,肝损害越重、其血清sICAM-1水平则越高。重肝患者肝衰竭越重,其血清sICAM-1水平反而越低,但仍显著高于轻、中度CHB和AsC。重肝早期患者血清sICAM-1水平显著高于中、晚期患者,中期患者血清sICAM-1水平也显著高于晚期患者。mq{&$, 百拇医药

    表 2 HBV感染者血清sICAM-1变化mq{&$, 百拇医药

    Tab 2 Changes of serum sICAM-1 in patients with HBV infection Groupsmq{&$, 百拇医药

    nmq{&$, 百拇医药

    sCIAM-1(ng/ml)mq{&$, 百拇医药

    AsCmq{&$, 百拇医药

    6

    219.7±59.0*h^9hcq, 百拇医药

    CHB(Mi)h^9hcq, 百拇医药

    9h^9hcq, 百拇医药

    367.9±118.5*h^9hcq, 百拇医药

    CHB(Mo)h^9hcq, 百拇医药

    9h^9hcq, 百拇医药

    613.9±128.9*h^9hcq, 百拇医药

    CHB(Se)h^9hcq, 百拇医药

    14h^9hcq, 百拇医药

    1273.4±404.4*h^9hcq, 百拇医药

    SH(E)h^9hcq, 百拇医药

    10h^9hcq, 百拇医药

    1413.3±167.6*△h^9hcq, 百拇医药

    SH(M)h^9hcq, 百拇医药

    12h^9hcq, 百拇医药

    1202.3±163.1h^9hcq, 百拇医药

    SH(L)h^9hcq, 百拇医药

    14h^9hcq, 百拇医药

    986.4±137.8h^9hcq, 百拇医药

    CHB(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 SHh^9hcq, 百拇医药

    *Compared with each other among 5 groups,P<0.01h^9hcq, 百拇医药

    Compared with each other among 3 groups,P<0.05

    2.3 CHB患者血清sICAM-1水平与肝功能的关系 CHB患者血清sICAM-1水平越高,其PTa则越低,两者间呈明显负相关(r=-0.4022,P<0.05)。CHB患者血清sICAM-1水平越高,其TSB也越高,两者间呈显示正相关(r=0.6997,P<0.01)。CHB患者血清sICAM-1水平与其血清AST之间呈显示正相关(r=0.3536,P<0.05),而与血清ALT之间无明显相关性(r=0.1808,P>0.05)。do, 百拇医药

    2.4 重肝患者血清sICAM-1水平与肝功能的关系 重肝患者血清sICAM-1水平越低,其PTa也越低,两者间呈显著正相关(r=0.6047,P<0.01);血清sICAM-1水平越低,共TSB越高,两者间呈显著负相关(r=-0.4483,P<0.01)。血清sICAM-1水平与血清ALT无显著相关(r=0.0167,P>0.05),也与血清AST无显著相关(r=0.0611,P>0.05)。do, 百拇医药

    3 讨论do, 百拇医药

    CHB患者肝组织的肝细胞膜均有不同程度ICAM-1表达,其表达强度与肝组织炎症坏死程度密切相关[1,2]。本研究发现,CHB患者血清sICAM-1水平明显高于正常人和慢性无症状HBsAg携带者,重肝患者血清sICAM-1水平明显高于CHB患者。说明乙型肝炎患者血清sICAM-1水平有不同程度升高,与其肝细胞膜有不同程度ICAM-1表达相一致。国外研究表明炎症性肝病患者血清sICAM-1至少有三个来源:①肝细胞合成释放sICAM-1;②由膜型ICAM-1裂解脱落而来;③细胞死亡后由肝细胞膜ICAM-1碎裂溶解入血[3,4]do, 百拇医药

    重度CHB患者血清sICAM-1水平明显高于中度CHB,中度CHB患者血清sICAM-1水平明显高于轻度CHB。说明血清sICAM-1与肝细胞膜ICAM-1表达水平一样,可作为反映CHB患者肝组织炎症和肝损害程度的指标。[5]do, 百拇医药

    本研究显示CHB患者血清sICAM-1水平越高,其血清总胆红素也就越高、凝血酶原活动度则越低,说明血清sICAM-1水平与肝功能一致性较好、能较好反映CHB患者的肝功能损害程度。do, 百拇医药

    重肝患者肝衰竭越重,肝组织坏死也越明显,残存肝细胞很少,肝细胞合成释放sICAM-1和凝血酶原也减少,处理胆红素的能力也降低,这就是重肝患者血清sICAM-1水平越低,其PTa也越低、TSB越高、肝衰竭越严重的原因之一;另外,重肝患者肝组织残存肝细胞较少,肝细胞膜ICAM-1表达的绝对量也就较少,因此由肝细胞膜ICAM-1脱落而来的ICAM-1也就减少。

    乙型肝炎患者肝组织中浸润的细胞毒性T细胞(CTL)表面有淋巴细胞功能相关抗原-1(LFA-1)表达,CTL能借助LFA-1与ICAM-1阳性HBV感染肝细胞粘附,攻击破坏肝细胞[6]。血清中的sICAM-1能封闭CTL表面的LFA-1,竞争抑制CTL攻击破坏靶细胞[7]。本研究显示,从无症状HBsAg携带者至重型肝炎早期,血清sICAM-1水平均随着肝损害的加重而升高;而在重型肝炎,血清sICAM-1水平反而随着肝损害的加重而降低,但仍显著高于中、轻度慢性肝炎。一方面说明血清sICAM-1水平升高是肝组织炎症坏死的结果,另一方面也显示重型肝炎患者血清sICAM-1水平降低对其病情是不利的。l, 百拇医药

    作者简介 第一作者:男,33岁,博士,讲师,主治医师l, 百拇医药

    参考文献l, 百拇医药

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    (1998-03-18收稿;1998-11-24修回)(张绪清 顾长海)