临床研究 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-10-15; 11(10): 1544-1546
在线出版日期: 2003-10-15. doi: 10.11569/wcjd.v11.i10.1544
肝病患者血清IGF-I和IGF-II的变化
邵静鸣, 俞丽芬, 张曙, 吴云林
邵静鸣, 昆山市第二人民医院消化科 江苏省昆山市 215300
邵静鸣, 男, 1963-06-30生, 浙江省湖州, 汉族. 1983年扬州医学院毕业, 主治医师.
俞丽芬, 张曙, 吴云林, 上海第二医科大学附属瑞金医院消化科 上海市 200025
基金项目: 日本Asahi医学发展项目基金资助.
通讯作者: 吴云林, 200025, 上海市瑞金二路197号, 上海市瑞金医院消化科. graceyu1028@sohu.com
电话: 021-64370045-665260 传真: 021-64150773
收稿日期: 2003-03-07
修回日期: 2003-03-20
接受日期: 2003-04-03
在线出版日期: 2003-10-15

目的

为了研究肝病患者血清IGF-I、IGF-II水平的变化及其临床意义.

方法

将89位肝病患者分成三组, 其中肝炎组10例, 肝硬化组66例, 肝癌组13例; 另设对照组38例. 应用放射免疫法测定患者血清IGF-I、IGF-II的含量.

结果

肝硬化患者组血清IGF I、IGF II的测值分别为65 14 mg/L, 32886 mg/L; 肝癌组为4914 mg/L, 19461 mg/L; 两组测值均显著低于对照组 (26175 mg/L, 1094119 mg/L). 肝硬化Child A 级患者的血清IGF-I 、IGF-II水平较Child B/C 级患者均明显增高(P<0.05). 血清IGF-I 、IGF-II值在不同病因的肝硬化患者之间亦存在显著差异 (P<0.05).

结论

与IGF-I一样, 血清IGF-II水平的测定同样可作为评价肝硬化、肝癌患者肝功能状况的一项重要指标.

关键词: N/A
引文著录: 邵静鸣, 俞丽芬, 张曙, 吴云林. 肝病患者血清IGF-I和IGF-II的变化. 世界华人消化杂志 2003; 11(10): 1544-1546
Serum levels of insulin-like growth factor (IGF)-I and II in patients with liver diseases
Jing-Ming Shao, Li-Fen Yu, Shu Zhang, Yun-Lin Wu
Jing-Ming Shao, Department of Gastroenterology, Kunshan Second Hospital, Kunshan 215300, Jiangsu Province, China
Li-Fen Yu, Shu Zhang, Yun-Lin Wu, Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China
Supported by: the Asahi Medical Development Fund of Japan.
Corresponding author: Dr. Li-Fen Yu, Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, 200025, Shanghai, China. graceyu1028@sohu.com
Received: March 7, 2003
Revised: March 20, 2003
Accepted: April 3, 2003
Published online: October 15, 2003

AIM

To investigate the serum levels and their clinical significance of insulin-like growth factor (IGF)-I, IGF-II in patients of liver diseases.

METHODS

89 patients with liver diseases were divided into three groups. hepatitis (n = 10), cirrhosis (n = 66) and liver cancer (n = 13) group. 38 healthy people were served as control group. The serum levels of IGF-I and IGF-II were measured by RIA.

RESULTS

The serum levels of IGF-I and IGF-II in cirrhotic group (65 ± 14 mg/L, 328 ± 86 mg/L, respectively) and cancer group (49 ± 14 mg/L, 194± 61 mg/L, respectively) were significantly lower than controls (261 ± 75 mg/L, 1 094 ±119 mg/L, respectively). In cirrhotic patients, IGF-I and IGF-II were significantly higher in Child A than those in Child B/C (P<0.05, respectively). The concentrations of IGF-I and IGF-II correlated significantly with different etiology of cirrhosis (P<0.05, respectively).

CONCLUSION

The serum level of IGF-II, as well as that of IGF-I, was an important index to assess the liver function of patients with cirrhosis or liver cancer.

Key Words: N/A
0 引言

血清胰岛素样生长因子(Insulin-like growth factor, IGF)-I是由70个氨基酸组成的多肽, IGF-II是由67个氨基酸组成的多肽, 在结构和功能与胰岛素相似, 可促进细胞的增生和生长, 在人体的分化和发育过程中起重要作用[1,2]. 肝病患者血清IGF-I和IGF-II的水平较正常人群低[3,4], IGF-I作为肝功能不良的早期标志物和/或判断肝硬化患者生存期的指标[5-7], 结果显示血清IGF-I水平与肝病患者的营养程度、内分泌等因素密切相关, 其正常值的范围较广, 在正常人群中的数值分布与年龄呈负相关; IGF-I水平的高低与Child-pugh分级有显著的相关关系. 通过重组人生长激素(rhGH)刺激后的IGF-I测定, 能显著地提高对患者生存期预测的准确性[8-12]. 当研究的重点转移到肝硬化患者对特异性的IGF结合蛋白的效应时[13-18], 仍然忽视了IGF-II的价值. 我们选择了病毒性肝炎、肝硬化和肝癌三种不同的肝病患者, 并以健康志愿者作为对照, 分别进行血清IGF-I和IGF-II水平的测定, 旨在探索IGF-II在不同类型的肝病患者血清中的浓度变化, 其与肝功能状态的相关程度及临床潜在价值.

1 材料和方法
1.1 材料

肝病患者89例, 其中慢性乙型肝炎患者10例(男8例, 女2例), 年龄21-41(平均26)岁; 肝硬化患者66例(男47例, 女19例), 年龄38-83(平均57)岁; 肝癌患者13例(均为男性), 年龄46-61(平均52)岁. 诊断符合1995年全国传染病与寄生虫病学术会议的诊断标准, 慢性乙型肝炎、肝硬化和肝癌的诊断均经肝组织活检、B超和CT证实. 健康对照组38例从体检者中获得(排除肝脏疾患), 男女各19例, 年龄36-60 (平均48岁). IGF-I试剂盒, 法国BECKMAN COULTER公司产品; IGF-II试剂盒, 美国DSL公司产品.

1.2方法

所有患者均询问病史, 进行常规体检和相关实验室检查(包括肝、肾功能、凝血酶元时间、血氨、AFP)以及B超、CT检查等. 清晨空腹采静脉血3 ml, 常规离心分离血清, 置于-40 °C低温冰箱保存待测. 标本处理及测试步骤均严格参照试剂说明书, 运用放射免疫法测定血清中IGF-I和IGF-II的含量(mg/L), 其中IGF-II测值根据说明书要求取log B/T值.

统计学处理 用SPSS软件进行统计处理. 计量数据以表示; 各组均数间的差异比较用方差分析法检验; 血氨值与IGF-I和IGF-II之间的关系用相关分析法检验; 各组临床症状、体征与IGF-I和IGF-II值的关系用t检验.

2 结果
2.1 肝病患者血清IGF-I和IGF-II水平

肝硬化和肝癌组患者的IGF-I、IGF-II明显低于健康对照组(P<0.001), 也明显低于慢性肝炎组(P<0.01, 表1). 肝炎组与健康对照组相比, 其测值无显著差异(P>0.05).

表1 肝病患者血清IGF-I和IGF-II测值的比较(mean±SD, mg/L).
分组nIGF-IIGF-II
肝炎10241±61985±111
肝硬化6665±14328±86
肝癌1349±14194±61
对照38260±751 094±119
2.2 肝硬化肝功能分级与IGF-I和IGF-II水平的关系

Child A级与Child B/C级患者的IGF-I和IGF-II水平均有显著性差异(P<0.01, 表2). 而Child B级与Child C级间患者的IGF-I和IGF-II水平无明显差异(P>0.05). IGF-I和IGF-II在有黄疸/肝掌的患者中较低, 而没有黄疸/肝掌体征的患者却有较高水平的表达(P<0.05, P<0.01, 表3). 有蜘蛛痣的患者其IGF-II表达较少, 与无蜘蛛痣的患者间存在显著的差异(P<0.05). 其他临床症状和体征的有无, 未见明显差异. 血氨大于184 mmol/L组的IGF-I为54±18 mg/L, IGF-II为293±68 mg/L; 血氨184 mmol/L组的IGF-I为74±22 mg/L, IGF-II为338±101 mg/L, 两组间无明显差异(P>0.05). 血氨值与IGF-I的相关分析结果为r = -0.43 (P<0.05), 与IGF-II的相关分析结果为r = -0.47(P<0.05).

表2 肝硬化患者的Child-pugh分级及相应的IGF-I、IGF-II水平比较 (mean±SD, mg/L).
肝硬化组nIGF-IIGF-II
Child A组18117±31497±130
Child B组3153±18340±83
Child C组1729±8206±61
表3 肝硬化患者临床症状体征与IGF-I和IGF-II的关系 (mean±SD, mg/L).
n乏力
腹胀
巩膜黄染
蜘蛛痣
肝掌
+-+-+-+-+-
51155412214536305115
IGF-I54 ±1868±1963±1872 ±1951 ±16a71 ±1866±1764±1857±16b91 ±24
IGF-II333 ±80311 ±64326 ±85365 ±69274±60 a354±87294 ±72a370±90304±72 a410 ±84
aP<0.05,
bP<0.01, vs (-).
2.3 肝硬化病因与IGF-I和IGF-II水平的关系

病毒性肝炎后与血吸虫性、酒精性及其他3组比较, IGF-I和IGF-II水平均显著降低(P<0.01).

3 讨论

Okan et al [13]发现IGF-I和IGF-Bp3与肝脏炎症的严重程度、纤维化或转氨酶活性无相关. 慢性肝炎患者IGF-I和IGF-Bp3水平与肝硬化患者有一定的差异, 在慢性肝炎进展为肝硬化之前血清IGF-I有高水平表达. Hayakawa et al [19]发现血清IGF-II在慢性肝炎、肝硬化和原发性肝癌的表达均比正常组明显减少. 我们的实验结果显示肝炎组与健康对照组相比, IGF-I和IGF-II水平无明显降低 (P>0.05); 而肝硬化组和肝癌组的IGF-I和IGF-II测值明显低于健康对照组(P<0.001), 与慢性肝炎组也有显著差异(P<0.01). IGF家族包括IGF-I、IGF-II、IGF-1R和IGFBPs, 在肝癌的发生发展中起了重要的作用[20-23]. IGF-II在肝癌中有较高的表达, 但是关于IGF-II的致癌机制, 目前仍不十分清楚, 比较一致的观点是肝癌细胞能自分泌大量的IGF-II, 直接作用于自身或邻近细胞的IGF-II受体, 产生胞质内短路循环, 加速或放大了细胞的IGF-II持续生长信号的传递. 我们测定的13例肝癌患者, 其IGF-II水平未见明显增高. Fan et al认为IGF-II和IGF-II mRNA在慢性肝炎、肝硬化和肝癌中均有不同程度的表达, 阳性率依次为: 慢性肝炎(33.3%)小于肝癌(66.7%)小于肝硬化(72.0%), 但在肝细胞再生结节、肝细胞不典型增生及分化较差的肝癌细胞中IGF-II和IGF-II mRNA表达最为显著. 提示IGF-II和IGF-IIR在肝细胞癌变的早期阶段即有表达, IGF-II和IGF-IIR在肝细胞癌变演化过程中起重要作用.

Kratzsch et al认为肝硬化患者血清中IGF-I (r = -0.64, P<0.001) 或IGF-Bp3 (r = -0.67, P<0.001) 水平与Child-Pugh分级密切相关, 肝硬化患者血清中IGF-I水平较正常人显著减少. 但Nikolic et al的试验显示血清IGF-I水平与肝硬化患者的Child-Pugh分级无明显相关, IGF-II与Child-Pugh分级有相关(P = 0.007), 血清IGF-II在Child A组的水平较Child B/C组明显增高. 从本研究结果可见Child B/C组患者的血清IGF-II水平较Child A组明显下降, 与Child A组的测值之间有显著性差异(P<0.01). 而Child B组与Child C组间患者的IGF-I、IGF-II水平无明显差异 (P>0.05). 提示血清IGF-II水平也能判断肝病患者的肝功能状况. Nikolic et al 又将肝硬化的患者按发病原因分成酒精性(n = 27)、病毒性(n = 17)和其他(n = 21)3组, 不同病因之间二者的测值无显著差异, 所以血清IGF-I、IGF-II水平与肝硬化病因之间无相关. 而本研究发现, 肝炎后肝硬化组的IGF-I和IGF-II水平均较其他病因导致的肝硬化明显降低, 有显著性差异(P<0.05). 提示血清IGF-I和IGF-II水平在病毒性肝硬化患者中可能具有一定的特异性. 肝硬化的严重程度与其临床症状密切相关, 目前尚未见国内外有评价血清IGF-I、IGF-II水平与肝硬化患者相应临床症状、体征关系的类似报道. 我们发现, 一些特异性的肝硬化症状、体征, 如黄疸、蜘蛛痣和肝掌的有无与血清IGF-I、IGF-II水平相关(P<0.05或P<0.01).

我们将肝病患者的血氨值与血清IGF-I和IGF-II水平进行比较发现, 血氨浓度大于正常值上限的组其IGF-I和IGF-II水平与血氨浓度正常组相比, 二者之间无明显差异(P>0.05), 但血氨与血清IGF-I和IGF-II水平呈负相关.

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