补肾生血方治疗慢性再生障碍性贫血的临床疗效及对T细胞亚群、T-bet与GATA3表达的影响

Clinical Effect of Bushen Shengxue Prescription on Chronic Aplastic Anemia and Its Effect on T Cell Subsets and Expression of T-bet and GATA3

目的:探讨补肾生血方与益气养血方治疗慢性再生障碍性贫血疗效及T细胞亚群与T-box家族的新型转录因子(T-bet)、Gata转录因子家族的转录因子3(GATA3)表达的影响。方法:收集2018年5月至2021年6月,在全国19家医院就诊的慢性再生障碍性贫血患者共585例,利用前瞻性、双盲、随机对照方法,采用分层区组随机法将患者分为3组,肾虚组、气血两虚组、对照组,中药治疗分别予补肾生血方颗粒、益气养血方颗粒、安慰剂(半量补肾生血方颗粒),均联合口服西药环孢素及雄激素。每组治疗以3个月为一疗程,连续观察2个疗程,分析治疗前后检测患者血常规,T细胞亚群及融合基因T-bet、GATA3,并监测安全性指标。结果:观察期间共脱落75例,剔除18例,最终肾虚组161例,气血两虚组164例,对照组167例,共492例完成治疗。治疗6个月后,肾虚组的总有效率98.8%(159/161)高于气血两虚组的79.9%(131/164)(χ^(2)=30.135,P<0.01);肾虚组明显高于对照组的总有效率61.7%(103/167)(χ^(2)=70.126,P<0.01);气血两虚组总有效率高于对照组(χ^(2)=13.232,P<0.01)。与本组治疗前比较,治疗后3组患者的血红蛋白(HGB)明显提升(P<0.05,P<0.01),且肾虚组HGB含量提高更为显著(P<0.01);治疗后与气血两虚组比较,肾虚组与对照组的白细胞(WBC)及血小板(PLT)均显著升高(P<0.01);3组患者治疗后的中性粒细胞(ANC)差异无统计学意义。3组患者在相同时间点进行比较,肾虚组T辅助细胞1(Th1)、Th1/Th2水平均明显降低(P<0.05),且肾虚组CD4^(+)水平明显下降,CD4^(+)/CD8^(+)明显降低(P<0.05)。肾虚组与其余两组CD19^_(-)、HLA/DR^(+)、CD25^(+)比较差异无统计学意义,肾虚组与对照组T-bet均低于气血两虚组(P<0.05)。结论:补肾生血方治疗再生障碍性贫血可能通过改善免疫调节机制,抑制免疫系统活性,调节T细胞亚群,抑制Th1及CD4^(+)水平,促进骨髓造血,且安全、不良反应小,方案值得进一步推广。

Objective:To investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells(T-bet)and GATA binding protein 3(GATA3).Method:A total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled.With the prospective,double-blind and randomized control methods,the patients were randomized into three groups:kidney deficiency group,Qi and blood deficiency group,and control group.The three groups were respectively treated with Bushen Shengxue prescription granule,Yiqi Yangxue prescription granule,and Placebo(half the dose of Bushen Shengxue formula granules).In addition,all of them were given oral cyclosporin and androgen.The treatment lasted 6 months,with 3 months as a course.The blood routine indexes,T cell subsets,and fusion genes T-bet and GATA3 before and after treatment were analyzed,and the safety indexes were monitored.Result:During the observation,a total of 75 cases dropped out and 18 were rejected.Finally,161cases in the kidney deficiency group,164 in the Qi and blood deficiency group,and 167 in the control group were included.After 6 months of treatment,the total effective rate was 98.8%(159/161) in the kidney deficiency group,which was higher than the 79.9%(131/164)in the Qi and blood deficiency group(χ^(2)=30.135,P<0.01)and the 61.7%(103/167)in the control group(χ^(2)=70.126,P<0.01).The total effective rate was higher in the Qi and blood deficiency group than in the control group(χ^(2)=13.232,P<0.01).After treatment,the hemoglobin(HGB)content increased significantly in three groups(P<0.05)as compared with that before treatment,particularly the kidney deficiency group(P<0.01).After treatment,the white blood cell(WBC)count and platelet(PLT)count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group(P<0.01).There was no specific difference in neutrophils(ANC)after treatment among the three groups.At the same time point,the level of T helper type 1(Th1)cells,Th1/Th2 ratio(P<0.05),level of CD4^(+),and CD4^(+)/CD8^(+) ratio(P<0.05)were significantly low in the kidney deficiency group among three groups.There was no significant difference in CD19-,HLA/DR+,and CD25^(+) between the kidney deficiency group and the other two groups,but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group(P<0.05).Conclusion:Bushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism,inhibiting the activity of immune system,modulating T cell subsets,suppressing Th1 and CD4^(+),and promoting bone marrow hematopoiesis.Moreover,it is safe with little side effects,which is worthy of further promotion.