补肾活血法与益气补肾法治疗慢性再生障碍性贫血的疗效比较

A clinical study on comparison of therapeutic effect of tonifying kidney and activating blood circulation method to that of replenishing qi and tonifying kidney method for treatment of patients with chronic aplastic anemia

目的比较补肾活血与补肾益气两种方法治疗慢性再生障碍性贫血（慢性再障）的疗效，探讨以补肾为基础的中药复方在慢性再障治疗中的优势。方法采用前瞻性研究方法，将90例慢性再障患者按随机数字表法分为补肾活血组、补肾益气组和西药对照组，每组30例。3组均给予对症支持治疗；西药对照组给予环孢素A3～5mg·kg-1·d-1，安雄80mg、每日2次或司坦唑醇2mg、每日3次口服；补肾活血组在对照组治疗基础上给予金匮肾气丸加减合活血中药（熟地黄15g，肉桂3g，淡附片4g，补骨脂12g，淫羊藿8g，杜仲12g，山茱萸15g，淮山药15g，枸杞子15g，制首乌12g，黄精15g，当归10g，赤芍10g，桃仁6g，鸡血藤10g），每日1剂；补肾益气组在对照组治疗基础上给予金匮肾气丸加减合益气中药（黄芪30g，炒白术10g，党参12g，熟地黄15g，肉桂3g，淡附片4g，补骨脂12g，淫羊藿8g，杜仲12g，山茱萸15g，淮山药15g，枸杞子15g，制首乌12g，黄精15g），每日1剂，3组均治疗6个月后观察血象、外周血淋巴细胞亚群、γ-干扰素（IFN-γ）、肿瘤坏死因子-α（TNF—α）的变化及临床疗效。结果3组治疗后白细胞计数（wBc）、血红蛋白（t／b）及血小板计数（PLT）均较治疗前明显增加[西药对照组：wBc（×109／L）：3．58±1．04比2．35±0．94，Hb（g／L）：83．60±22．31比65．43±23．20，PLT（×10^9／L）：60．43±30．54比36．84±20．12；补肾活血组：WBC（×10^9／L）：4．05±1．62比2．40±1．24，Hb（g／L）：95．25±19．64比68．57±26．59，PLT（×10^9/L）：72．65±37．76比40．23±20．01；益气补肾组：wBC（×10^9／L）：3．87±1．47比2．19±1．20，Hh（g/L）：89．64±27．43比62．11±20．21，PLT（×10^9／L）：69．54±40．21比38．67±18．34，均P〈0．05]；而3组间治疗前后比较差异均无统计学意义（均P〉0．05）；3组治疗后CD4＋均较治疗前增高，CD8＋均较治疗前减少，CD4＋／CD8＋比值较治疗前增大，且补肾活血组和益气补。肾组的变化较西药对照组更显著[CD4＋：（48．17±4．28）％、（50．28±3．68）％比（43．71±5．86）％，CD8＋：（18．52±6．20）％、（18．60±4．18）％比（21．96±6．64）％，CD4＋／CD8＋：（2．60±0．60）％、（2．70±0．38）％比（1｜99±0．52）％，均P〈O．05]；3组治疗前后CD3＋比较差异均无统计学意义（均P〉O．05）。3组治疗后血清IFN-γ、TNF-α水平均治疗前明显下降，且以补肾活血组和益气补肾组的下降较对照组更明显[IFN-γ（ng／L）：21．62±9．46、25．43±10．16比30．46±12．62，TNF—α（ng／L）：15．48±12．50、17．43±9．86比20．43±11．83，均P〈0．05]。补肾活血组和益气补肾组总有效率均较对照组明显升高[86．7％（26／30）、8313％（25／30）比66．7％（20／30），P〈0．05或P〈0．01]，但补肾活血组和益气补肾组总有效率比较差异无统计学意义（P〉O．05）。结论补肾活血法及益气补肾法能显著提高慢性再障患者的疗效，其机制可能是通过调节免疫功能、改善造血组织血供及降低造血负调控因子水平来实现。

Objective To compare the therapeutic effect of tonifying kidney and activating blood circulation method to that of replenishing qi and tonifying kidney method in treatment of patients with chronic aplastic anemia （CAA）, and to approach the advantage of Chinese medicine prescription based on tonifying kidney for treatment of CAA. Methods A prospective study was conducted. Ninety patients with CAA were randomly divided into tonifying kidney and activating blood circulation group, replenishing qi and tonifying kidney group and western medicine control group by a random number table, 30 cases in each group. All the patients in the three groups were given symptomatic treatment. And the patients in western medicine control group were treated with cyclosporine A 3 - 5 mg kg-1 d-1, andriol 80 mg twice daily or stanozolol 2 mg thrice a day orally. The patients in tonifying kidney and promoting blood circulation group were treated, on the basis of treatment in control group, additionally with modified Jinkui Shenqi pills plus Chinese herbal medicine for promoting blood circulation （Rehmanniae Radix Praeparata 15 g, Cinnamomi Cortex 3 g, Aconiti lateralis Radix Praeparata 4 g, Psoraleae Fructus 12 g, Epimedii Herba 8 g, Eucommiae Cnrlex 12 g, Corni Fructus 15 g, Dioscoreae Rhizoma 15 g, Lycii Fruetus 15 g, Polygoni Multiflori Radix Praeparata 12 g, Polygonati Rhizoma 15 g, Angelicae Sinensis Radix 10 g, Paeoniae Radix Rubra 10 g, Persicae Semen 6 g, Spatholobi Caulis 10 g）, one dose a day. The patients in replenishing qi and invigorating kidney group were treated, on the basis of treatment in the control group, additionally with modified Jinkui Shenqi pills plus traditional Chinese medicine for replenishing qi （Astragali seu Hedysari Radix 30 g, Atractylodis Macrocephalae Rhizoma Tostum 10 g, Codonopsis Radix 12 g, Rehmanniae Radix Praeparatal5 g, Cinnamomi Cortex 3 g, Aconiti lateralis Radix Praeparata 4 g, Aconiti lateralis Radix Praeparata 12 g, Epimedii Herba 8 g, Eucommiae Cortex 15 g, Corni Fruetus 15 g, Dioscoreae Rhizoma 15 g, Lycii Fructus 15 g, Polygoni Multiflori Radix Praeparata 12 g, Polygonati Rhizoma 15 g）, one dose daily. After treatment for 6 months, the changes of blood picture, subsets of lymphocytes in peripheral blood, γ-interferon （IFN-γ）, tumor necrosis factor-α （TNF-α） were observed, and the clinical efficacy was evaluated in the three groups. Results After treatment, the levels of white blood cell count （WBC）, hemoglobin （Hb） and platelet count （PLT） were increased significantly compared with those before treatment in three groups [western medicine control group： WBC （×10^9/L）： 3.58± 1.04 vs. 2.35 ± 0.94, Hb （g/L）： 83.60 ± 22.31 vs. 65.43 ±23.20, PLT （ x 109/L）： 60.43 ± 30.54 vs. 36.84 ±20.12; tonifying kidney and activating blood circulation group： WBC （ x 109/L）： 4.05 ± 1.62 vs. 2.40± 1.24, Hb （g/L）： 95.25 ±19.64 vs. 68.57±26.59, PLT （ x 109/L）： 72.65±37.76 vs. 40.23 ±20.01; replenishing qi and tonifying kidney group： WBC （x 109/L）： 3.87 ± 1.47 vs. 2.19± 1.20, Hb （g/L）： 89.64 ±27.43 vs. 62.11 ±20.21, PLT （x 109/L）： 69.54 ± 40.21 vs. 38.67 ± 18.34, all P 〈 0.05], no statistical significant differences were found before and after treatment among the three groups （all P 〉 0.05）. After treatment, in the three groups, the expression of CD4~ cells was higher than that before treatment, that of CD8＋ cells was reduced and the ratio of CD4＋/CD8＋ was increased compared with those before treatment, and the changes in tonifying kidney and activating blood circulation group and replenishing qi and tonifying kidney group were more significant than those in the control group [CD4＋： （48.17 ± 4.28）%, （50.28 ± 3.68）% vs. （43.71 ± 5.86）%, CD8＊： （18.52 ±6.20）%, （18.60 ±4.18）% vs. （21.96 ± 6.64）%, CD4＋/CD8＋： （2.60±0.60）%, （2.70 ±0.38）% vs. （1.99 ± 0.52）%, all P 〈 0.05], The expressions of CD3＋ cells in the three groups had no statistical significant differences between before and after treatment （all P 〉 0.05）. There was no significant difference in CD3＋ level between before and after treatment in three groups （all P 〉 0.05）. Compared with those before treatment, after treatment the levels of IFN- γ and TNF- α in serum were significantly decreased in the three groups, and the degree of descent in tonifying kidney and activating blood circulation group and replenishing qi and tonifying kidney group was more obvious than that in western medicine control group [IFN- γ （ng/L）： 21.62 ± 9.46, 25.43 ± 10.16 vs. 30.46 ±12.62, TNF-α（ng/L）： 15.48 ±12.50, 17.43 ± 9.86 vs. 20.43 ± 11.83, all P 〈 0.05]. The total clinical effective rates in tonifying kidney and activating blood circulation group and the replenishing qi and tonifying kidney group were markedly higher than those of western medicine control group [86.7% （26/30）, 83.3% （25/30） vs. 66.7% （20/30）, P 〈 0.05 or P 〈 0.01], but the comparison of the total clinical effective rate between the tonifying kidney and activating blood circulation group and replenishing qi and tonifying kidney group showed no statistically significant difference （P 〉 0.05）. Conclusions The tonifying kidney and activating blood circulation method and replenishing qi and tonifying kidney method applied for treatment of CAA can significantly elevate the curative effect. And their mechanisms are possibly related to the regulation of immune function, improvement of the blood supply of hematopoietic tissue and reduction of the levels of hematopoietic negative regulatory factors.