Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1检测及其临床意义
作者：王加林 赵亚平 周 玮 吴和军i^uk, 百拇医药
单位：解放军第82医院 江苏淮阴 223001i^uk, 百拇医药
关键词：可溶性细胞间粘附分子-1 可溶性血管细胞粘附分子-1 Ⅱ型糖尿病i^uk, 百拇医药
免疫学杂志990215 摘 要 应用酶联免疫吸附法(ELISA)，测定了47例Ⅱ型糖尿病患者和20例健康对照者血清可溶性细胞间粘附分子-1(sICAM-1)和可溶性血管细胞粘附分子-1(sVCAM-1)含量。结果表明：①血清sICAM-1和sVCAM-1水平，在Ⅱ型糖尿病组及有、无微血管病变组均显著高于健康对照组(P<0.05～0.01)，有微血管病变组又高于无微血管病变组(P<0.05～0.01)；②Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1之间呈正相关关系(r＝0.53，P<0.01)。提示：血清sICAM-1和sVCAM-1参与Ⅱ型糖尿病的发病过程。i^uk, 百拇医药
中图号 R587.1i^uk, 百拇医药
MEASUREMENT OF SERUM sICAM-1 AND sVCAM-1 IN TYPEⅡ DIABETIC PATIENTS AND ITS CLINICAL SIGNIFICANCEi^uk, 百拇医药
Wang Jialin，Zhao Yaping，Zhou Wei，Wu Hejuni^uk, 百拇医药
(The 82nd Hospital of PLA，Huaiyin 223001)i^uk, 百拇医药
Abstract The serum levels of soluble intercellular adhesion molecule-1(sICAM-1) and soluble vascular cell adhesion molecule-1(sVCAM-1) were measured with ELISA method in 47 cases of type 2 diabetic patients and 20 cases of healthy subjects.The results showed that：(1)The serum levels of sICAM-1 and sVCAM-1 in type Ⅱ diabetic patients and type 2 diabetic patients with and without microangiopathy were higher than those in healthy controls respectively(P<0.05～0.01)，serum levelsof sICAM-1 and sVCAM-1 in type Ⅱ diabetic patients with microangiopathy were much higher than those in type Ⅱ diabetic patients without microangiopathy(P<0.05～0.01)；(2)Serum levels of sICAM-1 in type Ⅱ diabetic patients had much positive correlation with serum levels of sVCAM-1(r＝0.53，P<0.01).These results suggested that the serum sICAM-1 and sVCAM-1 might participate in the course of type 2 diabetes mellitus.
Key words Soluble intercellular adhesion molecule-1，Soluble vascular cell adhesion molecule-1，Type 2 diabetes mellitusrd{s, 百拇医药
细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1)等细胞表面粘附分子对细胞间的相互作用具有重要作用[1，2]，其可溶性形式可溶性ICAM-1(sICAM-1)和可溶性VCAM-1(sVCAM-1)在糖尿病等疾病时表达增加，并具有一定的临床意义[3～5]。本文对47例Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1含量作了检测，现报道如下。rd{s, 百拇医药
1 对象和方法rd{s, 百拇医药
1.1 对象 糖尿病按1985年WHO提出的诊断标准确诊，为我院内分泌科住院患者。Ⅱ型糖尿病47例(男19，女28)，平均年龄50.2岁，病程6个月～16年。31例合并有糖尿病慢性微血管病变(糖尿病视网膜病变、肾脏病变和神经病变)为有微血管病变组，16例无慢性微血管病变为无微血管病变组；又按血清甘油三脂及血压正常与否分为高甘油三脂血症组(A组)18例，高甘油三脂血症合并高血压组(B组)10例，单纯高血压组(C组)8例，甘油三脂、血压正常组(D组)11例。以20例(男7，女13，平均年龄34.8a)本市中心血站健康献血员和本院工作人员作为对照组，检查无肝、肾、血液、肿瘤及糖尿病。rd{s, 百拇医药
1.2 方法rd{s, 百拇医药
1.2.1 血清sICAM-1和sVCAM-1检测：均采用酶联免疫吸附法(ELISA)，所用试剂盒购自法国Coulter公司。操作严格按说明书进行，简述如下：系列稀释的sICAM-1、sVCAM-1标准品和稀释的待测血清100μl加入96孔酶标板，再加生物素标记的抗sICAM-1或sVCAM-1抗体50μl，室温下孵育1h，洗涤液洗3次，每孔加100μl辣根过氧化物酶标记的链霉亲和素，室温下孵育20min。按常规加底物3，3’，5，5’-四甲基联苯胺(TMB)显色，于酶标仪(上海三科仪器有限公司产品，318MC型)上测各孔A450nm值。根据不同浓度的标准血清的A450nm值作标准曲线，计算待测标本血清sICAM-1和sVCAM-1浓度。
1.2.2 空腹血糖(FBG)：葡萄糖氧化酶法测定。3o7, http://www.100md.com
1.2.3 血清甘油三脂(TG)：常规方法测定。3o7, http://www.100md.com
1.3 统计学方法 采用t检验及直线相关分析法。3o7, http://www.100md.com
2 结果3o7, http://www.100md.com
2.1 47例Ⅱ型糖尿病患者和20例健康对照者血清sICAM-1、sVCAM-1和FBG测定 血清sICAM-1、sVCAM-1水平，Ⅱ型糖尿病组及有、无微血管病变组均显著高于健康对照组(P<0.05～0.01)，有微血管病变组又高于无微血管病变组(P<0.05～0.01)。见表1。3o7, http://www.100md.com
表1 Ⅱ型糖尿病患者和健康对照者血清sICAM-1、sVCAM-1和FBG测定(
±s)3o7, http://www.100md.com
Tab 1 Results of serum sICAM-1，sVCAM-1 and FBG between patients with type Ⅱ diabetes mellitus and controls(±s) Group3o7, http://www.100md.com
n3o7, http://www.100md.com
Serum sICAM-13o7, http://www.100md.com
(ng/ml)3o7, http://www.100md.com
Serum sVCAM-13o7, http://www.100md.com
(ng/ml)3o7, http://www.100md.com
FBG3o7, http://www.100md.com
(mmol/L)3o7, http://www.100md.com
Type Ⅱ diabetes mellitus(1)3o7, http://www.100md.com
473o7, http://www.100md.com
501.71±184.21△3o7, http://www.100md.com
848.18±232.72△
12.9±3.1△pj$!, http://www.100md.com
With microangiopathy(2)pj$!, http://www.100md.com
31pj$!, http://www.100md.com
524.69±158.61△**pj$!, http://www.100md.com
943.87±243.49△*pj$!, http://www.100md.com
14.1±2.2△pj$!, http://www.100md.com
without microangiopathy(3)pj$!, http://www.100md.com
16pj$!, http://www.100md.com
457.18±173.51△pj$!, http://www.100md.com
748.27±155.32△△pj$!, http://www.100md.com
10.7±2.5△pj$!, http://www.100md.com
Control(4)pj$!, http://www.100md.com
20pj$!, http://www.100md.com
300.51±68.73pj$!, http://www.100md.com
638.51±117.23pj$!, http://www.100md.com
5.1±0.5pj$!, http://www.100md.com
△P<0.01，*△△P<0.05，compared with 4；*P<0.01，**P<0.05，compared with 3pj$!, http://www.100md.com
2.2 Ⅱ型糖尿病患者血清sICAM-1、TG测定 A组和B组患者血清sVCAM-1显著高于C组和D组(P均<0.05)；A组和B组、C组和D组之间均无显著差异(P均>0.05)，见表2。pj$!, http://www.100md.com
表2 Ⅱ型糖尿病患者血清sVCAM-1和TG测定结果(±s)
Tab 2 Results of serum sVCAM-1 and triglycerides in patients with type Ⅱ diabetes mellitus(±s) Group2[cgw}[, http://www.100md.com
n2[cgw}[, http://www.100md.com
Serum sVCAM-1(ng/ml)2[cgw}[, http://www.100md.com
Triglycerides(mmol/L)2[cgw}[, http://www.100md.com
A2[cgw}[, http://www.100md.com
182[cgw}[, http://www.100md.com
844.92±188.95△*▲2[cgw}[, http://www.100md.com
2.72±0.7△*▲2[cgw}[, http://www.100md.com
B2[cgw}[, http://www.100md.com
102[cgw}[, http://www.100md.com
876.01±158.96△*2[cgw}[, http://www.100md.com
2.69±0.7△*2[cgw}[, http://www.100md.com
C2[cgw}[, http://www.100md.com
82[cgw}[, http://www.100md.com
741.79±148.24△△2[cgw}[, http://www.100md.com
1.37±0.2△△2[cgw}[, http://www.100md.com
D2[cgw}[, http://www.100md.com
112[cgw}[, http://www.100md.com
714.62±105.752[cgw}[, http://www.100md.com
1.12±0.32[cgw}[, http://www.100md.com
△P<0.05，△△P>0.05，compared with group D；2[cgw}[, http://www.100md.com
*P<0.05，compared with group C；
▲P>0.05，compared with group B；/7, 百拇医药
2.3 血清sICAM-1水平与sVCAM-1、FBG的关系 相关分析发现，47例Ⅱ型糖尿病患者血清sICAM-1与sVCAM-1呈显著正相关关系(r＝0.53，P<0.01)，血清sICAM-1、sVCAM-1与FBG之间无显著相关关系(P均>0.05)。/7, 百拇医药
3 讨论/7, 百拇医药
ICAM-1和VCAM-1是血管内皮细胞等细胞表面的粘附分子，属免疫球蛋白超家族分子，其膜外段裂解和廓清则分别形成sICAM-1和sVCAM-1。本研究结果显示：Ⅱ型糖尿病及有、无微血管病变患者血清sICAM-1和sVCAM-1均高于健康对照者，其中有微血管病变患者血清sICAM-1和sVCAM-1又高于无此并发症者，似说明此两可溶性粘附分子参与了Ⅱ型糖尿病发病的病理生理过程，并可作为病情变化的监测指标。/7, 百拇医药
研究还显示，Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1之间呈正相关关系，而它们与空腹血糖无相关关系，表明引起Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1变化的机制类似，但并非血糖升高的直接后果。本研究尚表明：Ⅱ型糖尿病合并高甘油三脂血症以及合并高甘油三脂血症、高血压患者的血清sVCAM-1显著高于合并单纯高血压患者和甘油三脂、血压正常者，且前两者之间和后两者之间的sVCAM-1水平无显著差异，提示Ⅱ型糖尿病患者血清sVCAM-1升高尚与高甘油三脂血症有关。/7, 百拇医药
据认为，蓄积在糖尿病患者血管系统内的糖化终产物(advanced glycation endproducts，AGEs)与内皮细胞VCAM-1表达和释放sVCAM-1增加有关，且sVCAM-1可作为糖尿病患者进展中的细胞功能紊乱的一个观察指标[4]，而AGEs对Ⅱ型糖尿病患者血清sICAM-1表达有无影响尚待进一步研究。/7, 百拇医药
作者简介 第一作者：男，41岁，本科，副主任医师/7, 百拇医药
参考文献/7, 百拇医药
1 Springer TA.Adhesion receptors of the immune system.Nature，1990，345：425/7, 百拇医药
2 Carlos TM，Harlan JM.Leukocyte-endothelial adhesion molecules.Blood，1994，84：2068/7, 百拇医药
3 Ceriello A，Falleti E，Bortolotti N，et al.Increased circulating intercellular adhesion molecule-1 levels in type Ⅱ diabetic patients：the possible role of metabolic control and oxidative stress.Metabolism，1996，45(4)：498/7, 百拇医药
4 Schmidt AM，Crandall J，Hori O，et al.Elevated plasma levels of vascular cell adhesion molecule-1(VCAM-1) in diabetic patients with microalbuminuria：a marker of vascular dysfunction and progressive vascular disease.Br J Haematol，1996，92(3)：747/7, 百拇医药
5 Shimizu Y，Minemura M，Tsukishiro T. Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression.Hepatology，1995，22(2)：525/7, 百拇医药
(1998-06-26收稿；1998-09-29修回)(王加林 赵亚平 周 玮 吴和军)
单位：解放军第82医院 江苏淮阴 223001i^uk, 百拇医药
关键词：可溶性细胞间粘附分子-1 可溶性血管细胞粘附分子-1 Ⅱ型糖尿病i^uk, 百拇医药
免疫学杂志990215 摘 要 应用酶联免疫吸附法(ELISA)，测定了47例Ⅱ型糖尿病患者和20例健康对照者血清可溶性细胞间粘附分子-1(sICAM-1)和可溶性血管细胞粘附分子-1(sVCAM-1)含量。结果表明：①血清sICAM-1和sVCAM-1水平，在Ⅱ型糖尿病组及有、无微血管病变组均显著高于健康对照组(P<0.05～0.01)，有微血管病变组又高于无微血管病变组(P<0.05～0.01)；②Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1之间呈正相关关系(r＝0.53，P<0.01)。提示：血清sICAM-1和sVCAM-1参与Ⅱ型糖尿病的发病过程。i^uk, 百拇医药
中图号 R587.1i^uk, 百拇医药
MEASUREMENT OF SERUM sICAM-1 AND sVCAM-1 IN TYPEⅡ DIABETIC PATIENTS AND ITS CLINICAL SIGNIFICANCEi^uk, 百拇医药
Wang Jialin，Zhao Yaping，Zhou Wei，Wu Hejuni^uk, 百拇医药
(The 82nd Hospital of PLA，Huaiyin 223001)i^uk, 百拇医药
Abstract The serum levels of soluble intercellular adhesion molecule-1(sICAM-1) and soluble vascular cell adhesion molecule-1(sVCAM-1) were measured with ELISA method in 47 cases of type 2 diabetic patients and 20 cases of healthy subjects.The results showed that：(1)The serum levels of sICAM-1 and sVCAM-1 in type Ⅱ diabetic patients and type 2 diabetic patients with and without microangiopathy were higher than those in healthy controls respectively(P<0.05～0.01)，serum levelsof sICAM-1 and sVCAM-1 in type Ⅱ diabetic patients with microangiopathy were much higher than those in type Ⅱ diabetic patients without microangiopathy(P<0.05～0.01)；(2)Serum levels of sICAM-1 in type Ⅱ diabetic patients had much positive correlation with serum levels of sVCAM-1(r＝0.53，P<0.01).These results suggested that the serum sICAM-1 and sVCAM-1 might participate in the course of type 2 diabetes mellitus.
Key words Soluble intercellular adhesion molecule-1，Soluble vascular cell adhesion molecule-1，Type 2 diabetes mellitusrd{s, 百拇医药
细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1)等细胞表面粘附分子对细胞间的相互作用具有重要作用[1，2]，其可溶性形式可溶性ICAM-1(sICAM-1)和可溶性VCAM-1(sVCAM-1)在糖尿病等疾病时表达增加，并具有一定的临床意义[3～5]。本文对47例Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1含量作了检测，现报道如下。rd{s, 百拇医药
1 对象和方法rd{s, 百拇医药
1.1 对象 糖尿病按1985年WHO提出的诊断标准确诊，为我院内分泌科住院患者。Ⅱ型糖尿病47例(男19，女28)，平均年龄50.2岁，病程6个月～16年。31例合并有糖尿病慢性微血管病变(糖尿病视网膜病变、肾脏病变和神经病变)为有微血管病变组，16例无慢性微血管病变为无微血管病变组；又按血清甘油三脂及血压正常与否分为高甘油三脂血症组(A组)18例，高甘油三脂血症合并高血压组(B组)10例，单纯高血压组(C组)8例，甘油三脂、血压正常组(D组)11例。以20例(男7，女13，平均年龄34.8a)本市中心血站健康献血员和本院工作人员作为对照组，检查无肝、肾、血液、肿瘤及糖尿病。rd{s, 百拇医药
1.2 方法rd{s, 百拇医药
1.2.1 血清sICAM-1和sVCAM-1检测：均采用酶联免疫吸附法(ELISA)，所用试剂盒购自法国Coulter公司。操作严格按说明书进行，简述如下：系列稀释的sICAM-1、sVCAM-1标准品和稀释的待测血清100μl加入96孔酶标板，再加生物素标记的抗sICAM-1或sVCAM-1抗体50μl，室温下孵育1h，洗涤液洗3次，每孔加100μl辣根过氧化物酶标记的链霉亲和素，室温下孵育20min。按常规加底物3，3’，5，5’-四甲基联苯胺(TMB)显色，于酶标仪(上海三科仪器有限公司产品，318MC型)上测各孔A450nm值。根据不同浓度的标准血清的A450nm值作标准曲线，计算待测标本血清sICAM-1和sVCAM-1浓度。
1.2.2 空腹血糖(FBG)：葡萄糖氧化酶法测定。3o7, http://www.100md.com
1.2.3 血清甘油三脂(TG)：常规方法测定。3o7, http://www.100md.com
1.3 统计学方法 采用t检验及直线相关分析法。3o7, http://www.100md.com
2 结果3o7, http://www.100md.com
2.1 47例Ⅱ型糖尿病患者和20例健康对照者血清sICAM-1、sVCAM-1和FBG测定 血清sICAM-1、sVCAM-1水平，Ⅱ型糖尿病组及有、无微血管病变组均显著高于健康对照组(P<0.05～0.01)，有微血管病变组又高于无微血管病变组(P<0.05～0.01)。见表1。3o7, http://www.100md.com
表1 Ⅱ型糖尿病患者和健康对照者血清sICAM-1、sVCAM-1和FBG测定(
±s)3o7, http://www.100md.comTab 1 Results of serum sICAM-1，sVCAM-1 and FBG between patients with type Ⅱ diabetes mellitus and controls(
±s) Group3o7, http://www.100md.comn3o7, http://www.100md.com
Serum sICAM-13o7, http://www.100md.com
(ng/ml)3o7, http://www.100md.com
Serum sVCAM-13o7, http://www.100md.com
(ng/ml)3o7, http://www.100md.com
FBG3o7, http://www.100md.com
(mmol/L)3o7, http://www.100md.com
Type Ⅱ diabetes mellitus(1)3o7, http://www.100md.com
473o7, http://www.100md.com
501.71±184.21△3o7, http://www.100md.com
848.18±232.72△
12.9±3.1△pj$!, http://www.100md.com
With microangiopathy(2)pj$!, http://www.100md.com
31pj$!, http://www.100md.com
524.69±158.61△**pj$!, http://www.100md.com
943.87±243.49△*pj$!, http://www.100md.com
14.1±2.2△pj$!, http://www.100md.com
without microangiopathy(3)pj$!, http://www.100md.com
16pj$!, http://www.100md.com
457.18±173.51△pj$!, http://www.100md.com
748.27±155.32△△pj$!, http://www.100md.com
10.7±2.5△pj$!, http://www.100md.com
Control(4)pj$!, http://www.100md.com
20pj$!, http://www.100md.com
300.51±68.73pj$!, http://www.100md.com
638.51±117.23pj$!, http://www.100md.com
5.1±0.5pj$!, http://www.100md.com
△P<0.01，*△△P<0.05，compared with 4；*P<0.01，**P<0.05，compared with 3pj$!, http://www.100md.com
2.2 Ⅱ型糖尿病患者血清sICAM-1、TG测定 A组和B组患者血清sVCAM-1显著高于C组和D组(P均<0.05)；A组和B组、C组和D组之间均无显著差异(P均>0.05)，见表2。pj$!, http://www.100md.com
表2 Ⅱ型糖尿病患者血清sVCAM-1和TG测定结果(
±s)Tab 2 Results of serum sVCAM-1 and triglycerides in patients with type Ⅱ diabetes mellitus(
±s) Group2[cgw}[, http://www.100md.comn2[cgw}[, http://www.100md.com
Serum sVCAM-1(ng/ml)2[cgw}[, http://www.100md.com
Triglycerides(mmol/L)2[cgw}[, http://www.100md.com
A2[cgw}[, http://www.100md.com
182[cgw}[, http://www.100md.com
844.92±188.95△*▲2[cgw}[, http://www.100md.com
2.72±0.7△*▲2[cgw}[, http://www.100md.com
B2[cgw}[, http://www.100md.com
102[cgw}[, http://www.100md.com
876.01±158.96△*2[cgw}[, http://www.100md.com
2.69±0.7△*2[cgw}[, http://www.100md.com
C2[cgw}[, http://www.100md.com
82[cgw}[, http://www.100md.com
741.79±148.24△△2[cgw}[, http://www.100md.com
1.37±0.2△△2[cgw}[, http://www.100md.com
D2[cgw}[, http://www.100md.com
112[cgw}[, http://www.100md.com
714.62±105.752[cgw}[, http://www.100md.com
1.12±0.32[cgw}[, http://www.100md.com
△P<0.05，△△P>0.05，compared with group D；2[cgw}[, http://www.100md.com
*P<0.05，compared with group C；
▲P>0.05，compared with group B；/7, 百拇医药
2.3 血清sICAM-1水平与sVCAM-1、FBG的关系 相关分析发现，47例Ⅱ型糖尿病患者血清sICAM-1与sVCAM-1呈显著正相关关系(r＝0.53，P<0.01)，血清sICAM-1、sVCAM-1与FBG之间无显著相关关系(P均>0.05)。/7, 百拇医药
3 讨论/7, 百拇医药
ICAM-1和VCAM-1是血管内皮细胞等细胞表面的粘附分子，属免疫球蛋白超家族分子，其膜外段裂解和廓清则分别形成sICAM-1和sVCAM-1。本研究结果显示：Ⅱ型糖尿病及有、无微血管病变患者血清sICAM-1和sVCAM-1均高于健康对照者，其中有微血管病变患者血清sICAM-1和sVCAM-1又高于无此并发症者，似说明此两可溶性粘附分子参与了Ⅱ型糖尿病发病的病理生理过程，并可作为病情变化的监测指标。/7, 百拇医药
研究还显示，Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1之间呈正相关关系，而它们与空腹血糖无相关关系，表明引起Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1变化的机制类似，但并非血糖升高的直接后果。本研究尚表明：Ⅱ型糖尿病合并高甘油三脂血症以及合并高甘油三脂血症、高血压患者的血清sVCAM-1显著高于合并单纯高血压患者和甘油三脂、血压正常者，且前两者之间和后两者之间的sVCAM-1水平无显著差异，提示Ⅱ型糖尿病患者血清sVCAM-1升高尚与高甘油三脂血症有关。/7, 百拇医药
据认为，蓄积在糖尿病患者血管系统内的糖化终产物(advanced glycation endproducts，AGEs)与内皮细胞VCAM-1表达和释放sVCAM-1增加有关，且sVCAM-1可作为糖尿病患者进展中的细胞功能紊乱的一个观察指标[4]，而AGEs对Ⅱ型糖尿病患者血清sICAM-1表达有无影响尚待进一步研究。/7, 百拇医药
作者简介 第一作者：男，41岁，本科，副主任医师/7, 百拇医药
参考文献/7, 百拇医药
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3 Ceriello A，Falleti E，Bortolotti N，et al.Increased circulating intercellular adhesion molecule-1 levels in type Ⅱ diabetic patients：the possible role of metabolic control and oxidative stress.Metabolism，1996，45(4)：498/7, 百拇医药
4 Schmidt AM，Crandall J，Hori O，et al.Elevated plasma levels of vascular cell adhesion molecule-1(VCAM-1) in diabetic patients with microalbuminuria：a marker of vascular dysfunction and progressive vascular disease.Br J Haematol，1996，92(3)：747/7, 百拇医药
5 Shimizu Y，Minemura M，Tsukishiro T. Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression.Hepatology，1995，22(2)：525/7, 百拇医药
(1998-06-26收稿；1998-09-29修回)(王加林 赵亚平 周 玮 吴和军)