摘要：
Objective To investigate the effect of immunosuppressive therapy (IST ) on the expression of serum tumor necrosis factor (TNF)-α,interferon-γ,soluble Fas (sFas)and peripheral blood T cell subsets in patients with aplastic anemia (AA).Methods From June 2016 to June 2018,a total of 50 patients with AA admitted to Rugao People's Hospital were selected as study group.The patients in study group were (28.8±4.6)years old.There were 24 male and 26 female patients.There were 27 cases of severe aplastic anemia (SAA)and 23 cases of very severe aplastic anemia (VSAA).At the same time, a total of 50 healthy individuals who were (29.2±4.8)years old and underwent physical examination in the same hospital were selected as control group,randomly.There were 23 male and 27 female subjects. Patients in study group were treated with cyclosporine and antithymocyte globulin (ATG)for IST.After 28 weeks of treatment,the clinical efficacy of patients with AA was evaluated.The levels of serum TNF-α, interferon-γ,sFas and T cell subsets in peripheral blood before and after treatment in study group and the subjects in control group were examined at physical examination time.Independent sample t test was used to compare the expression levels of TNF-α,interferon-γ,sFas and the proportions and proportion ratios of T cell subsets of subjects in the 2 groups and AA patients before and after treatment.The study protocol was approved by the Ethical Review Board of Investigation in Human at Rugao People's Hospital (Approval No.2016LL018).Informed consents were obtained from all participants.Results ① After 28 weeks of IST, twenty two cases of AA patients in study group basically cured,twenty cases were relieved,and 8 cases were significantly improved.The total effective rate was 84％ (42/50).② Before treatment,serum TNF-αand interferon-γlevels in study group were (170.7 ±22.4)pg/mL and (76.9 ± 5.9)pg/mL,respectively, and were significantly higher than those of (140.0±18.8)pg/mL and (52.4±4.8)pg/mL in control group, and the differences were statistically significant (t = 7.423,P < 0.001;t = 22.777,P < 0.001 ).Before treatment,serum sFas level in study group was (3.7±0.9)μg/L,and was significantly lower than that of (5.1 ± 1.0)μg/L in control group,and the difference was statistically significant (t = 7.358,P < 0.001 ). Serum TNF-αand interferon-γlevels in study group after treatment were (152.5±20.7)pg/mL and (61.5± 4.9)pg/mL,respectively,and were significantly lower than those of (170.7 ±22.4)pg/mL and (76.9 ± 5.9)pg/mL before treatment,and the differences were statistically significant (t =4.220,P < 0.001;t =14.199,P <0.001 );serum sFas level was (4.9 ± 1.0 )μg/L,and was significantly higher than that of (3.7±0.9)μg/L before treatment,and the difference was statistically significant (t = 6.307,P < 0.001 ).③ Proportions of CD3 + T cells,CD4 + T cells and CD4 + T cells/CD8 + T cells in study group were (61.5± 5.2)％,(28.8±5.0)％ and (1.2±0.4)％,respectively,and were significantly lower than those of (66.2 ± 4.9)％,(42.1±5.3)％ and (1.5±0.5)％ in control group,and the differences were statistically significant (t =4.651,P <0.001;t =12.907,P <0.001;t =3.313,P =0.001).Proportion of CD8 + T cells was (31.5 ± 5.0)％,and was significantly higher than that of (25.1 ± 5.2 )％ in control group,and the difference was statistically significant (t =6.273,P <0.001 ).The proportions of CD3 + T cells,CD4 + T cells and CD4 +T cells/CD8 + T cells in study group after treatment were (64.9±5.0)％,(38.7±5.3)％ and (1.4±0.5)％, respectively,and were significantly higher than those of (61.5 ±5.2)％,(28.8 ±5.0)％ and (1.2 ±0.4)％before treatment,and the differences were statistically significant (t = 3.333,P < 0.001;t = 9.608,P <0.001;t =2.209,P =0.030);proportion of CD8 + T cells was (27.7 ±5.2)％,and was significantly lower than that of (31.5±5.0)％ before treatment,and the difference was statistically significant (t =3.725,P <0.001).Conclusions Expression levels of TNF-α,interferon-γ and proportion of CD8 + T cells in patients with AA were higher than those in healthy people,and the levels of sFas,proportions of CD3 + T cells, CD4 + cells and CD4 + T cells/CD8 + T cells were lower than those in healthy people.IST can significantly regulate the levels of serum TNF-α,interferon-γ,sFas and peripheral blood T cell subsets in patients with AA.%目的 探讨免疫抑制疗法(IST)对再生障碍性贫血(AA)患者血清肿瘤坏死因子(TNF)-α、γ干扰素、可溶性Fas(sFas)表达水平,以及外周血T细胞亚群比例的影响.方法 选择2016年6月至2018年6月,于如皋市人民医院接受住院治疗的50例AA患者为研究对象,纳入研究组.研究组患者年龄为(28.8±4.6)岁;男性患者为24例,女性为26例;重型再生障碍性贫血(SAA)患者为27例,极重型再生障碍性贫血(VSAA)为23例.随机选取同期于本院接受体检的50例健康个体纳入对照组,受试者年龄为(29.2±4.8)岁;男性受试者为23例,女性为27例.研究组患者给予环孢素与抗胸腺细胞球蛋白(ATG)进行IST,治疗28周后评估AA患者临床疗效.研究组患者于治疗前、后,对照组受试者于体检时抽取静脉血,检测血清TNF-α、γ干扰素、sFas水平,以及外周血T细胞亚群比例、比值.采用独立样本t检验比较2组受试者及AA患者治疗前、后血清TNF-α、γ干扰素、sFas表达水平,以及外周血T细胞亚群比例、比值.本研究经如皋市人民医院伦理委员会批准(批准文号:2016LL018).征得2组受试者的知情同意,并与之签署临床研究知情同意书.结果 ①研究组AA患者接受IST治疗28周后,22例获得基本治愈,20例获得缓解,8例明显进步,总有效率为84％(42/50).②研究组患者治疗前血清TNF-α、γ干扰素水平分别为(170.7±22.4)pg/mL、(76.9±5.9)pg/mL,均显著高于对照组的(140.0±18.8)pg/mL、(52.4±4.8)pg/mL,并且差异均有统计学意义(t=7.423,P<0.001;t=22.777,P<0.001);研究组患者治疗前sFas水平为(3.7±0.9)μg/L,显著低于对照组的(5.1±1.0)μg/L,并且差异亦有统计学意义(t=7.358,P<0.001);研究组患者治疗后血清TNF-α、γ干扰素水平分别为(152.5±20.7)pg/mL、(61.5±4.9)pg/mL,显著低于治疗前的(170.7±22.4)pg/mL、(76.9±5.9)pg/mL,并且差异均有统计学意义(t=4.220,P<0.001;t=14.199,P<0.001);治疗后sFas水平为(4.9±1.0)μg/L,显著高于治疗前的(3.7±0.9)μg/L,并且差异亦有统计学意义(t=6.307,P<0.001).③研究组患者治疗前外周血CD3+T细胞比例、CD4+T细胞比例及CD4+T细胞/CD8+T细胞分别为(61.5±5.2)％、(28.8±5.0)％、(1.2±0.4)％,均显著低于对照组的(66.2±4.9)％、(42.1±5.3)％、(1.5±0.5)％,并且差异均有统计学意义(t=4.651,P<0.001;t=12.907,P<0.001;t=3.313,P=0.001);CD8+T细胞比例为(31.5±5.0)％,显著高于对照组的(25.1±5.2)％,并且差异亦有统计学意义(t=6.273,P<0.001).研究组患者治疗后CD3+T细胞比例、CD4+T细胞比例及CD4+T细胞/CD8+T细胞分别为(64.9±5.0)％、(38.7±5.3)％、(1.4±0.5)％,均显著高于治疗前的(61.5±5.2)％、(28.8±5.0)％、(1.2±0.4)％,并且差异均有统计学意义(t=3.333,P<0.001;t=9.608,P<0.001;t=2.209,P=0.030);CD8+T细胞比例为(27.7±5.2)％,显著低于治疗前的(31.5±5.0)％,并且差异亦有统计学意义(t=3.725,P<0.001).结论 AA患者的TNF-α、γ干扰素表达水平及CD8+T细胞比例高于健康人群,sFas表达水平、CD3+T细胞比例、CD4+T细胞比例及CD4+T细胞/CD8+T细胞低于健康人群.IST能够显著调节AA患者的血清TNF-α、γ干扰素、sFas表达水平及外周血T细胞亚群数量.
