抑郁症患者血清补体通路差异蛋白的研究

Exploration of Differential Complement Pathway Proteins in Serum of Depressive Patients

目的探究补体差异蛋白与抑郁症的潜在联系。方法选取2015年1月至2016年7月大庆市第三医院收治的22例抑郁症患者作为抑郁症组,并纳入20例大庆市健康市民作为健康组,提取血清。利用同位素相对标记与绝对定量(i TRAQ)技术和独创通路分析(IPA)通路富集,得到补体通路及其补体通路中的差异表达蛋白。用酶联免疫吸附测定法(ELISA)对差异表达蛋白进行验证。从基因表达数据库(GEO)中获取重度抑郁症患者和健康人全血基因表达芯片数据集GSE19738,各21例。采用R包对数据做预处理和差异性表达基因(DEGs)的筛选,应用ClueGO进行生物过程富集分析。结果用ELISA验证出5个蛋白在抑郁症组中的表达显著升高,分别是补体因子I(CFI)、补体成分(C)2、C4A、C5、C6。对芯片数据集GSE98793分析,得到442个DEGs,其中102个基因表达上调,340个基因表达下调。经过ClueGO富集分析得到差异表达基因在生物过程中,主要参与翻译蛋白靶向到膜,线粒体呼吸链复合体组装,凋亡细胞;在细胞组成中,差异基因主要参与核糖体亚基,线粒体内膜。在分子功能方面,主要参与细胞色素C氧化酶活性,RNA聚合酶1活性,蛋白质通道活性。结论抑郁症患者血清补体通路中5个差异表达蛋白(CFI、C2、C4A、C5和C6)的表达量显著增加。这些差异补体蛋白可能与抑郁症存在密切联系,为疾病的病因、诊断和药物研究提供重要线索。

Objective To explore the potential relationship between differential complenlent proteins and depression. Methods Serum samples were collected from 22 patients with depression in the Daqing Third Hospital and 20 healthy peo-ple in Daqing during Jan. 2015 and Jul. 2016. Differentially expressed proteins in complement system were obtained by using isobaric tag for relative and absolute quantitation（iTRAQ） technique and ingenuity pathway analysis（IPA）. Enzyme-linked immune sorbent assay （ELISA） was employed to identify differentially expressed serum？ proteins of complement sys-tem of the healthy volunteers （ n = 20） and patients with depression （ n = 22）. Then, microarray gene expression dataset GSE19738 was searched from gene expression omnibus（GEO） database which included 21 major depressive disorder and 21 control samples. Differentially expressed genes（DEGs） were screened using the limma package in R. ClueGO was used for bioprocess enrichment analysis. Results This studies revealed that levels of complement factor I （ CFI ）, complement component（ C）2, CdA, C5 and C6 were considerably increased in depressed patients compared to the healthy controls. A total of 442 DEGs were identified from the microarray data, including 102 up-regulated genes and 340 clown-regulated genes. Through ClueGO enrichment analysis,we found that differentially expressed genes were mainly involved in the targe-ting of translation proteins to the membrane, mitochondrial respiratory chain complex assembly, and apoptotic cells in biolo-gical process. The differential genes mainly participated in ribosomal subunits and mitochondrial intima in cell composition. In the aspect of molecular function, it was mainly involved in the activity of cytochrome C oxidase and RNA polymerase 1, and the activity of protein channel. Conclusion Five differentially expressed proteins（ CFI, C2, CdA, C5 and C6） in corn-plement system are significantly increased in the depressive patients. These differential complement proteins may be closely related to depression and provide important clues for the research on the etiology, diagnosis and drugs.