Jiang Hongjuan, Zhang Xuan, Chi Xiangyu, Wang Jianping, Wang Jing, Dou Jianming
Department of Healthcare, Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021, China. Email:
Department of Healthcare, Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2014 Apr;37(4):274-8.
To screen the biomarkers which may play important roles in the pathogenesis and therapy of asthma by using serum comparative proteomics.
From June 2011 to September 2012, 30 chronic persistent asthmatic patients (asthma group) and 30 healthy controls (control group) were selected for study in our hospital. All the asthmatic patients were given 8 week-treatment with inhaled glucocorticoids (ICS). Then comparative proteomics were employed to identify differential proteins in serum samples from the control group, the asthma pre-treatment group and the asthma post-treatment group. The differential proteins which had significant differences before and after ICS therapy were selected for Western blot analysis and ELISA detection. Besides, the correlation between the differential proteins and IgE, eosinophils (EOS), neutrophil percentage(NEUT%), and FEV1% were analyzed.
Eleven differential proteins were identified. Among them, heat shock protein 70 (HSP70), eosinophil chemotactic protein (Eotaxin) and vitamin D binding protein (VDBP) had significant differences in protein abundance before and after treatment. The differential expression of the 3 proteins in each group was confirmed by Western blot. ELISA data showed that the serum levels of HSP70 and Eotaxin were significantly higher in the asthma pre-treatment group [(439 ± 103)ng/L, (183 ± 79)ng/L] than those in the control group [(209 ± 58)ng/L, (91 ± 46)ng/L] (t = 5.281, 4.972, all P < 0.01), but significantly lower in the asthma post-treatment group[(247 ± 96) ng/L, (105 ± 58)ng/L] than those in the pre-treatment group (t = 4.157, 3.892, all P < 0.01). However, the serum level of VDBP was significantly lower in the asthmatics pre-treatment group [(318 ± 115)mg/L] than that in the control group [(541 ± 98)mg/L] (t = 3.878, P < 0.01), but significantly higher in the asthma post-treatment group[(479 ± 132)mg/L] than that in the pre-treatment group(t = 3.572, P < 0.01). The correlation analysis showed that HSP70 was correlated positively with IgE and NEUT%, but negatively with FEV1% (r = 0.568, 0.613, -0.516, all P < 0.01). Eotaxin was correlated positively with IgE and EOS, but negatively with FEV1% (r = 0.752, 0.826, -0.618, all P < 0.01). VDBP was correlated negatively with NEUT%, but positively with FEV1% (r = -0.537, 0.426, all P < 0.05).
HSP70, Eotaxin, and VDBP may participate in the pathogenesis of asthma, and may become the potential targets for ICS therapy.
运用血清比较蛋白质组学筛选出可能在哮喘发病机制及治疗中发挥重要作用的生物标志物。
2011年6月至2012年9月，选取我院30例慢性持续性哮喘患者（哮喘组）和30例健康对照者（对照组）进行研究。所有哮喘患者均接受8周吸入糖皮质激素（ICS）治疗。随后采用比较蛋白质组学方法鉴定对照组、哮喘治疗前组和哮喘治疗后组血清样本中的差异蛋白质。选取ICS治疗前后有显著差异的差异蛋白质进行蛋白质印迹分析和酶联免疫吸附测定（ELISA）检测。此外，分析差异蛋白质与免疫球蛋白E（IgE）、嗜酸性粒细胞（EOS）、中性粒细胞百分比（NEUT%）及第一秒用力呼气容积占预计值百分比（FEV1%）之间的相关性。
鉴定出11种差异蛋白质。其中，热休克蛋白70（HSP70）、嗜酸性粒细胞趋化蛋白（Eotaxin）和维生素D结合蛋白（VDBP）在治疗前后蛋白质丰度有显著差异。通过蛋白质印迹法证实了每组中这3种蛋白质的差异表达。ELISA数据显示，哮喘治疗前组血清HSP70和Eotaxin水平[(439 ± 103)ng/L，(183 ± 79)ng/L]显著高于对照组[(209 ± 58)ng/L，(91 ± 46)ng/L]（t = 5.281，4.972，均P < 0.01），但哮喘治疗后组[(247 ± 96) ng/L，(105 ± 58)ng/L]显著低于治疗前组（t = 4.157，3.892，均P < 0.01）。然而，哮喘治疗前组血清VDBP水平[(318 ± 115)mg/L]显著低于对照组[(541 ± 98)mg/L]（t = 3.878，P < 0.01），但哮喘治疗后组[(479 ± 132)mg/L]显著高于治疗前组（t = 3.572，P < 0.01）。相关性分析显示，HSP70与IgE和NEUT%呈正相关，但与FEV1%呈负相关（r = 0.568，0.613， -0.516，均P < 0.01）。Eotaxin与IgE和EOS呈正相关，但与FEV1%呈负相关（r = 0.752，0.826， -0.618，均P < 0.01）。VDBP与NEUT%呈负相关，但与FEV1%呈正相关（r = -0.537，0.426，均P < 0.05）。
HSP70、Eotaxin和VDBP可能参与哮喘的发病机制，且可能成为ICS治疗的潜在靶点。
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