环磷酰胺联合他克莫司影响狼疮性肾炎患者T细胞和IL-17水平变化的临床研究

Effect of cyclophosphamide combined with tacrolimus on T cell and IL-17 levels in patients with lupus nephritis

目的探讨环磷酰胺联合他克莫司对狼疮性肾炎患者T细胞和白细胞介素-17(IL-17)水平的影响。方法前瞻性选择2018年5月至2020年5月亳州市人民医院收治的76例狼疮性肾炎患者,按照随机数字表法分为2组,各38例。2组患者均接受糖皮质激素治疗,在此基础上,对照组加用环磷酰胺治疗,研究组加用环磷酰胺联合他克莫司治疗,共6个月。评价2组患者的临床疗效,治疗前、治疗6个月后采用流式细胞术检测外周血CD3^(+)T细胞、CD4^(+)辅助性T淋巴细胞(CD4^(+)Th)、CD8^(+)抑制性T淋巴细胞(CD8^(+)Ts)及IL-17水平,并观察不良反应发生情况。结果研究组总有效率(94.7%)明显高于对照组(78.9%),差异有统计学意义(P<0.05)。治疗前,2组患者的CD3^(+)T细胞、CD4^(+)Th、CD8^(+)Ts及CD4^(+)Th/CD8^(+)Ts比值,差异均无统计学意义(P>0.05),2组治疗6个月后CD3^(+)T细胞、CD4^(+)Th、CD8^(+)Ts及CD4^(+)Th/CD8^(+)Ts比值均较治疗前明显改善,差异均有统计学意义(P<0.05),且研究组[(66.29±13.51)%、(43.53±8.39)%、(31.66±3.37)%、1.31±0.25]明显优于对照组[(60.78±9.46)%、(38.77±7.42)%、(36.80±5.26)%、1.05±0.33],差异均有统计学意义(P<0.05)。治疗前,2组患者的血清IL-17水平差异无统计学意义(P>0.05),2组治疗6个月后血清IL-17水平均较治疗前明显降低,差异均有统计学意义(P<0.05),且研究组[(6.41±2.04)×10^(15)g/L]明显低于对照组[(9.52±3.11)×10^(15)g/L],差异有统计学意义(P<0.05)。研究组患者不良反应(13.2%)与对照组(21.1%)比较,差异无统计学意义(P>0.05)。结论环磷酰胺联合他克莫司治疗狼疮性肾炎可更有效地调节T细胞亚群,降低血清IL-17水平,协同纠正免疫紊乱,这是其增进临床疗效的重要机制。

Objective To investigate the effect of cyclophosphamide combined with tacrolimus on T cells and interleukin-17(IL-17) levels in patients with lupus nephritis. Methods From May 2018 to May 2020,76 patients with lupus nephritis admitted to Bozhou People’s Hospital were prospectively selected and divided into 2 groups according to a random number table,with 38 cases in each group. Both groups were treated with glucocorticoid. On this basis,the control group was treated with cyclophosphamide,and the study group was treated with cyclophosphamide combined with tacrolimus. The course of treatment were 6 months. The clinical efficacy was evaluated,the levels of CD3^(+)T cells,CD4^(+)helper T cells(CD4^(+)Th),CD8^(+)suppressor T cells(CD8^(+)Ts) and IL-17 in peripheral blood were detected by flow cytometry before and after 6 months of treatment,and the occurrence of adverse reactions was observed. Results The total effective rate of the study group(94. 7%)was significantly higher than that of the control group(78. 9%),the difference was statistically significant(P<0.05). Before treatment,there was no significant difference in CD3^(+)T cells,CD4^(+)Th,CD8^(+)Ts and CD4^(+)Th/CD8^(+)Ts ratio between the two groups(P>0.05). After 6 months of treatment,CD3^(+)T cells,CD4^(+)Th,CD8^(+)Ts and CD4^(+)Th/CD8^(+)Ts ratio of the two groups were significantly improved,the differences were statistically significant(P<0.05),and the study group[(66. 29 ± 13. 51) %,(43. 53 ± 8. 39) %,(31. 66 ± 3. 37) %,1. 31 ±0. 25] were significantly better than those of the control group[(60. 78 ± 9. 46) %,(38. 77 ± 7. 42) %,(36. 80 ± 5. 26) %,1. 05 ± 0. 33],the differences were statistically significant(P<0.05). Before treatment,there was no significant difference in serum IL-17 levels between the two groups(P>0.05). After 6 months of treatment,the levels of serum IL-17 in the two groups were significantly improved,the differences were statistically significant(P<0.05),and the study group [(6. 41 ± 2. 04) × 10^(15) g/L] was significantly better than that in the control group[(9. 52 ± 3. 11) × 1015 g/L],the difference was statistically significant(P<0.05). There was no significant difference in adverse reactions between the study group(13. 2%) and the control group(21. 1%)(P>0.05). Conclusion Cyclophosphamide combined with tacrolimus in the treatment of lupus nephritis can more effectively regulate T cell subsets,reduce serum IL-17 levels,and coordinate the correction of immune disorders,which is an important mechanism to improve the clinical efficacy.