摘要
目的:通过观察免疫性血小板减少症(ITP)患者大剂量地塞米松治疗前后T淋巴细胞中吲哚胺2,3-双加氧酶(IDO)和色氨酰-t RNA合成酶(TTS)的表达、血浆中色氨酸(Trp)和犬尿氨酸(Kyn)浓度的变化,探讨IDO/TTS介导的色氨酸代谢途径在ITP发病与治疗中的作用。方法:初诊或复发ITP患者与健康志愿者(对照组)各20例,患者采用地塞米松40 mg/d×4 d的标准方案治疗,在患者治疗前和治疗后第5天采集肝素抗凝血标本。液相-质谱联用分析系统(LC-MS/MS)检测血浆中Trp和Kyn浓度,流式细胞仪检测CD4+、CD8+T细胞中IDO和TTS的表达。结果:与对照组相比,ITP患者治疗前血浆Trp、Kyn浓度、Kyn/Trp比值明显增高(P<0.05);CD4+、CD8+T细胞中IDO的表达明显减低(P<0.05),而TTS的表达显著升高(P<0.05)。治疗有效组血浆Trp浓度较治疗前降低(P<0.05),但Kyn浓度和Kyn/Trp比值较治疗前都升高(P<0.05);CD4+、CD8+T细胞中IDO的表达高于治疗前(P<0.05),而TTS的表达较治疗前显著降低(P<0.05)。无效组治疗前后无明显差异。结论:IDO/TTS介导的色氨酸代谢途径与ITP的发病有关,通过检测IDO与TTS的水平可以了解患者对激素治疗的敏感性,从而指导临床用药。
Objective To discuss the role of indoleamine 2, 3-dioxygenas e （IDO） and tryptophanyl-tRNA synthetase （TTS） mediated tryptophan catabolism in immune thrombocytopenia （ITP） patients treated with high doses of dexamethasone through the expressions of IDO and TTS in T cells , and the concentrations of plasma kynurenine and tryptophan. Methods 20 newly diagnosed or relapse ITP patients were treated with 40 mg/d · 4 d dose of dexamethasone. The heparin anticoagulant blood samples were obtained before treatment and the 5th day after treatment. 20 healthy subjects were selected as the control group. The IDO and TTS expressions in CD4＋and CD8＋ T cells were analyzed by flow cytometry. The concentrations of plasma kynurenine and tryptophan were detected by liquid-mass spectrometry system. Results Compared with healthy controls group, the plasma tryptophan and kynurenine concentration and the ratio of Kyn/Trp were significantly elevated in ITP patients （P 〈0.05）; the IDO expressions of CD4＋ and CD8＋ T cells in ITP patients were significantly lower than those in healthy controls （P 〈 0.05）, but the TTS expressions were significantly higher （P 〈 0.05）. The concentration of tryptophan in effective group was significantly lower than before treatment （P 〈 0.05）, in contrast, the kynurenine concentration and the ratio of Kyn/Trp were significantly higher than before （P 〈 0.05）. The expression of IDO in effective group were significantly higher than that before treatment （P 〈 0.05）, conversely, the expression of TTS in effective group were significantly decreased （P 〈 0.05）. No significant difference can be found in ineffective group. Conclusion IDO/TTS-mediated tryptophan catabolism pathway could indicate the onset of ITP. The sensitivity of ITP patients with high dose of dexamethasone treatment can be observed through the level of IDO and TTS.
出处
《实用医学杂志》
CAS
北大核心
2014年第21期3441-3444,共4页
The Journal of Practical Medicine
基金
广东省科技厅基金资助项目(编号:2012B031800198)
