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原发性免疫性血小板减少症(immune thrombocytopenia,ITP)是一种由自身抗体免疫介导血小板过度破坏所引起的血小板减少性疾病。病人可有体液免疫和细胞免疫异常,导致B淋巴细胞产生破坏血小板的抗体及CD8+细胞毒T细胞破坏血小板、使血小板生成障碍,是ITP的经典发病机制。目前ITP治疗首选以地塞米松为主的糖皮质激素治疗,但停药后极易复发[1]。血小板生成素(TPO)受体激动剂可有效促进ITP病人骨髓巨核细胞的生成,迅速升高血小板,具有耐受性好、不良反应轻等优点[2],临床上重组人血小板生成素(rhTPO)应用最为广泛。研究[3-4]显示,人体免疫系统中辅助性T细胞(Th)可参与多种自身免疫性疾病的发生及发展,ITP病人也存在多种其他细胞免疫功能异常,T细胞功能紊乱可能在ITP的发病中起重要作用。有研究[5]发现,TPO受体激动剂能显著改善ITP病人的T细胞功能。本研究观察rhTPO联合大剂量地塞米松治疗对ITP病人的疗效及其对调节性T细胞(Treg)和Th1细胞、Th2细胞的表达影响。现作报道。
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观察组治疗总有效率为90.48%,高于对照组的67.50%(P<0.05)(见表 1)。
分组 n 完全反应 有效 无效 总有效 uc P 对照组 40 18(45.00) 9(22.50) 13(32.50) 27(67.50) 2.37 <0.05 观察组 42 28(66.67) 10(23.81) 4(9.52) 38(90.48) 合计 82 46(56.10) 19(23.17) 17(20.73) 65(79.27) 表 1 2组病人疗效比较[n;百分率(%)]
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治疗前,2组各项指标比较差异均无统计学意义(P>0.05)。治疗后,2组Treg细胞及Th2细胞均较治疗前明显上调(P<0.01),Th1细胞、Th1/Th2比例均较治疗前明显下降(P<0.01),且观察组Treg细胞及Th2细胞均明显高于对照组,Th1细胞、Th1/Th2均明显低于对照组(P<0.01)(见表 2)。
分组 n Treg Th1 Th2 Th1/Th2 治疗前 对照组 40 1.39±0.62 24.85±5.01 0.75±0.29 32.61±5.38 观察组 42 1.41±0.65 25.12±4.92 0.72±0.33 32.47±5.12 t — 0.14 0.25 0.44 0.12 P — >0.05 >0.05 >0.05 >0.05 治疗后 对照组 40 4.68±1.33** 18.16±2.72** 1.11±0.38** 20.46±3.19** 观察组 42 6.59±1.64** 13.23±3.56** 1.53±0.49** 14.15±2.16** t — 5.78 7.02 4.32 10.44# P — <0.01 <0.01 <0.01 <0.01 #示t′值;组内配对t检验:**P<0.01 表 2 2组病人治疗前后Treg、Th1、Th2细胞水平及Th1/Th2比例比较(x±s)
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治疗期间,对照组病人出现血糖升高4例,高血压2例,不良反应发生率为15.00%(6/40);观察组病人出现血糖升高3例,低钾血症2例,不良反应发生率为11.90%(5/42),2组不良反应发生率差异无统计学意义(χ2=5.72,P>0.05)。
重组人血小板生成素联合大剂量地塞米松对原发性ITP病人Treg细胞及Th1、Th2细胞的影响
Effect of the recombinant human thrombopoietin combined with high dose dexamethasone on the Treg cells, Th1 cells and Th2 cells in primary immune thrombocytopenia patients
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摘要:
目的观察重组人血小板生成素(rhTPO)联合大剂量地塞米松方案对原发性免疫性血小板减少症(ITP)病人调节性T细胞(Treg)及辅助性T细胞(Th)1、Th2表达水平的影响。 方法选择ITP病人82例,按照随机数字表法分为对照组40例和观察组42例。对照组给予大剂量地塞米松治疗,观察组在对照组治疗基础上加用rhTPO治疗。比较2组病人疗效,并采用流式细胞仪检测2组治疗前后Treg细胞和Th1、Th2细胞表达水平及Th1/Th2比例。 结果观察组病人疗效优于对照组(P < 0.05)。治疗前,2组病人Treg细胞和Th1、Th2细胞表达水平及Th1/Th2比例差异均无统计学意义(P>0.05);治疗后,2组病人Treg细胞及Th2细胞均较治疗前明显上调(P < 0.01),Th1细胞和Th1/Th2比例均较治疗前明显下降(P < 0.01),且观察组Treg细胞及Th2细胞表达水平均明显高于对照组(P < 0.01),Th1细胞和Th1/Th2均明显低于对照组(P < 0.01)。 结论rhTPO联合大剂量地塞米松治疗原发性ITP能通过增加病人Treg细胞数量、纠正Th1/Th2细胞平衡,提高临床疗效。 -
关键词:
- 原发性免疫性血小板减少症 /
- 重组人血小板生成素 /
- 地塞米松 /
- 调节性T细胞 /
- 辅助性T细胞
Abstract:ObjectiveTo observe the effects of recombinant human thrombopoietin(rhTPO) combined with high dose dexamethasone on the expression levels of CD4+CD25+Foxp3+regulatory T cells(Treg), T-helper 1(Th1) cells and T-helper 2(Th2) cells in primary immune thrombocytopenia(ITP) patients. MethodsEighty-two patients with ITP were divided into the control group(40 cases) and observation group(42 cases) according to the random number table method.The control group was treated with high-dose dexamethasone, and the observation group was treated with rhTPO on the basis of the control group.The therapeutic effects were compared between two groups.The expression levels of Treg cells, Th1 cells and Th2 cells, and the ratio of Th1/Th2 in two groups before and after treatment were detected using flow cytometry. ResultsThe total effective rate in observation group was significantly better than that in control group(P < 0.05).Before treatment, there was no statistical significance in the expression levels of Treg cells, Th1 cells and Th2 cells, and the ratio of Th1/Th2 between two groups(P>0.05).After treatment, the levels of Treg cells and Th2 cells were significantly up-regulated (P < 0.01), and the ratio of Th1 cells and Th1/Th2 decreased significantly compared with before treatment(P < 0.01).After treatment, the expression levels of Treg cells and Th2 cells in observation group were significantly higher than those in control group(P < 0.01), and the Th1 cells and Th1/Th2 ratio in observation group were significantly lower than those in control group(P < 0.01). ConclusionsThe rhTPO combined with high dose dexamethasone in the treatment of ITP can improve the clinical therapeutic effects through increasing the number of Treg cells and correcting the balance of Th1/Th2 cells. -
表 1 2组病人疗效比较[n;百分率(%)]
分组 n 完全反应 有效 无效 总有效 uc P 对照组 40 18(45.00) 9(22.50) 13(32.50) 27(67.50) 2.37 <0.05 观察组 42 28(66.67) 10(23.81) 4(9.52) 38(90.48) 合计 82 46(56.10) 19(23.17) 17(20.73) 65(79.27) 表 2 2组病人治疗前后Treg、Th1、Th2细胞水平及Th1/Th2比例比较(x±s)
分组 n Treg Th1 Th2 Th1/Th2 治疗前 对照组 40 1.39±0.62 24.85±5.01 0.75±0.29 32.61±5.38 观察组 42 1.41±0.65 25.12±4.92 0.72±0.33 32.47±5.12 t — 0.14 0.25 0.44 0.12 P — >0.05 >0.05 >0.05 >0.05 治疗后 对照组 40 4.68±1.33** 18.16±2.72** 1.11±0.38** 20.46±3.19** 观察组 42 6.59±1.64** 13.23±3.56** 1.53±0.49** 14.15±2.16** t — 5.78 7.02 4.32 10.44# P — <0.01 <0.01 <0.01 <0.01 #示t′值;组内配对t检验:**P<0.01 -
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