血清糖类抗原125水平在支气管扩张症患者中的临床意义

Serum carbohydrate antigen-125 levels in patients with bronchiectasis

Jing-hua GU , ¹ Yi-jun QIU , ¹ Yi-hua LU , ¹ Xu-dong XU , ¹ and Zhi-hao XU ^2, ^*

Jing-hua GU

1 舟山市普陀区人民医院呼吸科, 浙江舟山 316100

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Yi-jun QIU

1 舟山市普陀区人民医院呼吸科, 浙江舟山 316100

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Yi-hua LU

1 舟山市普陀区人民医院呼吸科, 浙江舟山 316100

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Xu-dong XU

1 舟山市普陀区人民医院呼吸科, 浙江舟山 316100

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Zhi-hao XU

2 浙江大学医学院附属第四医院, 浙江义乌 322000 1 舟山市普陀区人民医院呼吸科, 浙江舟山 316100 2 浙江大学医学院附属第四医院, 浙江义乌 322000

Corresponding author.

^{moc.361@536502hjghjg

第一作者：顾靖华(1981-), 男, 硕士, 主治医师, 主要从事呼吸系统常见疾病诊治; E-mail:; http://orcid.org/0000-0002-7416-9656
⁹
/L, 明显高于CA125正常组[(7.73±3.46)×10
⁹
/L], 差异有统计学意义(

P

< 0.05);CA125升高组患者外周血CRP中位数水平为22.98(3.18~196.88) mg/L, 高于CA125正常组[6.34(0.50~97.66) mg/L], 差异有统计学意义(

P

< 0.05)。相关性分析结果表明, 患者血清CA125水平与白细胞计数、CRP水平呈正相关(均

P

< 0.05), 进一步多元逐步回归分析显示CRP水平是CA125的独立影响因素。支气管扩张症患者治疗前后血清CA125水平差异有统计学意义(

P

< 0.05)。}

结论

支气管扩张症患者血清CA125水平升高, 经抗感染治疗后CA125水平下降, CRP水平是其独立影响因素。

Abstract

Objective

To evaluate the level of serum carbohydrate antigen-125(CA125) and its related factors in patients with bronchiectasis.

Methods

The clinical data of 504 patients with bronchiectasis in Zhejiang Putuo People's Hospital from June 2009 to June 2014 were collected in the study.The patients were divided into CA125 elevated group and CA125 normal group according to serum CA125 level, and the differences of serum CA125, age, gender, white blood cell(WBC), C-reactive protein(CRP), blood glucose and other test indicators were compared between two groups.

Results

There were 276 patients including 117 male and 159 female with elevated serum CA125.Their mean age was(66.3±13.1) years and the mean level of CA125 was(83.70±43.87) U/mL. There were 228 patients including 84 male and 144 female with normal CA125 levels. Their mean age was(67.5±10.5) years and the mean level of CA125 was(20.68±9.67) U/mL.The peripheral blood WBC in patients with CA125 elevated group[(10.08±5.68)×10 ⁹ /L] was significantly higher than that in CA125 normal group[7.73±3.46)×10 ⁹ /L], the difference was statistically significant( P < 0.05).The medium of CRP level in patients with CA125 elevated group[22.98(3.18~196.88) mg/L] was significantly higher than that in CA125 normal group[6.34(0.50~97.66) mg/L]( P < 0.05). Correlation analysis showed that CA125 was positively correlated with WBC and CRP( P < 0.05). Stepwise regression analysis showed that CRP was the only independent prognostic factors of CA125. Paired t test showed the presence of CA125 serum in patients with bronchiectasis had a significant difference between before and after anti-infection therapy( P < 0.05).

Conclusion

The serum levels of CA125 rise in patients with bronchiectasis, while it decrease after anti-infection therapy.CRP is an independent associated factor of serum CA125 level.

Keywords: Bronchiectasis, CA-125 Antigen/blood, C-reactive protein

糖类抗原125(CA125) 是一种糖蛋白，最初主要应用于卵巢癌的诊断和预后，近年来研究发现血清CA125在许多非恶性疾病中均可升高，如心功能不全、慢性肾病、浆膜腔积液、肝硬化、肺结核等。我们临床工作中发现很多支气管扩张症患者中血清CA125水平亦呈不同程度的升高。但是关于血清CA125与支气管扩张症两者之间关系相关报道较少。本研究通过比较血清CA125升高和正常的支气管扩张症患者的临床资料的差异，以及CA125升高患者治疗前后血清CA125的变化，探讨血清CA125在支气管扩张症中的临床意义。

根据2010年英国胸科协会非囊性纤维化支气管扩张指南标准，入选2009年6月至2014年6月在舟山市普陀区人民医院住院的504例支气管扩张症患者，排除合并妇科疾病、妊娠、肝硬化、心功能不全、慢性肾病、浆膜腔积液、活动性肺结核及恶性肿瘤患者。

根据血清CA125水平，将支气管扩张症患者分为CA125升高组和CA125正常组。血清CA125升高组276例，其中男性117例，女性159例，平均年龄(66.31±13.13) 岁，血清CA125水平为(83.70±43.87) U/mL；血清CA125正常组228例，男性84例，女性144例，平均年龄(67.54±10.50) 岁，血清CA125水平为(20.68±9.67) U/mL。

所有患者均清晨空腹采集静脉血，采用电化学发光免疫分析法(Cobas e601，德国罗氏公司)检测CA125，其参考值范围0~35 U/mL。其中CA125升高组276例患者治疗后予复查血清CA125。采用酶法(Cobas c701，德国罗氏公司)检测空腹血糖，其参考值范围3.9~6.1 mmol/L；采用五分类法(XE2100d，日本Sysmex公司)测定血白细胞计数，其参考值范围(4.0~10.0)×10 ⁹ /L；采用免疫比浊法(德国罗氏公司)检测C反应蛋白(C-reactive protein，CRP)，其参考值范围0~5 mg/L。

采用SPSS 17.0统计学软件进行统计。符合正态分布的计量资料用均数±标准差( s )表示，两组之间正态分布的连续性变量比较采用 t 检验；非正态分布采用中位数表示，两组之间比较采用非参数秩和检验，前后自身对照采用配对 t 检验，两组率之间的比较采用 ² 检验。相关分析采用Pearson或Spearman相关分析，对相关变量纳入回归方程，采用逐步回归分析。以 P ＜0.05为差异有统计学意义。

两组支气管扩张症患者年龄、性别、空腹血糖水平的差异均无统计学意义，而血白细胞、CRP、CA125均明显高于正常组( P ＜0.05)，见表 1 。表1 支气管扩张症患者血清CA125升高组与CA125正常组临床参数比较 Table 1 Comparison in patients with bronchiectasis between elevated CA125 group and normal CA125 group M(min~max) ]

年龄(岁)

男性/女性

CA125(U/mL)

白细胞数(×10 ⁹ /L)

CRP(mg/L)

空腹血糖(mmol/L)

CA125升高组

66.31±13.13

117/159

83.70±43.87

10.08±5.68

22.98(3.18~196.88)

6.76±3.81

CA125正常组

67.54±10.50

84/144

20.68±9.67

7.73±3.46

6.34(0.50~97.66)

5.83±1.57

-0.647

0.535

12.273

3.158

-4.415

1.969

0.519

0.465

0.000

0.002

0.000

0.051

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相关性分析结果显示，CA125与患者血清白细胞计数和CRP均呈正相关(均 P ＜0.05)，而与患者年龄、性别、血糖水平无相关性，见表 2 。表2 支气管扩张症患者血清CA125水平与各参数的相关性分析 Table 2 Correlation analysis between CA125 level and the parameters of patients with bronchiectasis

统计学参数

0.065

-0.024

0.211

0.270

0.109

0.406

0.761

0.006

0.000

0.161

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以CA125作为因变量，白细胞数和CRP作为自变量，进行多元逐步回归分析，得到回归方程：CA125=35.324+0.765×白细胞数+0.241×CRP。多元逐步回归分析表明，CRP是支气管扩张症患者CA125的唯一独立影响因素，见表 3 。表3 支气管扩张症患者血清CA125水平影响因素多元逐步回归分析 Table 3 Multivariate stepwise regression analysis of CA125 level in patients with bronchiectasis

95%可信区间

46.842

6.318

0.000

38.465~56.307

0.249

0.071

0.000

0.112~0.434

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276例CA125升高患者治疗后血清CA125水平为(47.34±27.01) U/mL，明显低于治疗前[(83.70±43.87) U/mL]，差异有统计学意义( t =12.717， P ＜0.05)；但仍高于CA125水平正常组[(20.68±9.67) U/mL]，差异有统计学意义( t =5.674， P ＜0.05)。

CA125是一种高分子量的黏蛋白样糖蛋白，存在于体腔上皮起源的各种组织以及这些组织发生的肿瘤中，是常用于检测妇科及消化道肿瘤的重要指标。Barbieri 应用其单克隆抗体经免疫组织化学染色研究证实：CA125存在于正常胚胎体腔上皮来源的组织中，如间皮细胞(包括胸膜、腹膜、心包膜)及输卵管、子宫内膜及宫颈内膜，同时也分布于支气管黏膜上皮。

本研究提示CA125与白细胞、CRP均呈正相关，进一步多元逐步回归分析表明CRP是支气管扩张症患者CA125的唯一独立影响因素，提示CRP在其中起到了至关重要的作用。众所周知，CRP是急性炎症患者血清中常见的一种急性时相蛋白，由TNF、IL-6、IL-1等细胞因子诱导肝脏细胞产生研究发现活动期溃疡性结肠炎患者的CRP及CAl25水平存在协同关系，而国外有学者报道在非感染性疾病如恶性卵巢肿瘤中CRP与CA125水平亦存在正相关。结合本研究结果，支气管扩张症患者急性感染时的炎症反应以支气管管腔内中性粒细胞募集及支气管壁和肺组织内中性粒细胞、单核巨噬细胞、肥大细胞、CD4 ⁺ T细胞浸润为特征，这些炎症细胞释放多种细胞因子，包括IL-16、IL-8、IL-10、TNF-α及内皮素-1等。值得注意的是，在临床工作中我们发现，社区获得性肺炎同样是支气管、肺泡组织的炎性病变，多数患者存在CRP升高，但很少发现有血清CA125升高患者。这一点说明除了CRP介导以外还存在其他因素导致支气管扩张症患者血清CA125水平异常。本研究还发现支气管扩张症患者治疗后血清CA125下降，提示急性炎症控制后CA125表达减少，进一步支持CRP独立影响血清CA125这一结论。但是感染控制后支气管扩张症患者血清CA125水平仍高于正常值，这一点仅仅从与CRP的关系亦难以解释。

支气管扩张症本质是一种常见的慢性呼吸道疾病，其基本病变是由于支气管及其周围肺组织的慢性炎症所导致的一支或多支支气管管壁损坏变形和不可逆性的扩张。其中，60%~80%的稳定期支气管扩张症患者存在潜在致病菌的定植，最常分离出的细菌为流感嗜血杆菌和铜绿假单孢菌。正是基于支气管扩张症发病机制，我们推测在CA125升高的支气管扩张症患者中除了CRP这个因素之外，定植菌特别是铜绿假单胞菌可能扮演了关键的角色，导致支气管上皮细胞CA125持续异常的表达。

综上所述，本研究过程中还存在不少不足之处，主要是尚未阐明CRP、CA125以及细胞因子三者之间具体作用机制。但是本研究尝试探讨了血清CA125水平与支气管扩张症之间联系，明确CRP为CA125独立影响因素，但其具体机制仍有待于进一步深入研究。

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