Xu Wencheng, Meng Kehan, Kusano Junichi, Matsuda Hiroto, Hara Yoshikazu, Fujii Yoshiaki, Suzuki Shinya, Ando Eiki, Wang Xiaoqin, Tu Yuanchao, Tanaka Sachiko, Sugiyama Kentaro, Yamada Haruki, Hirano Toshihiko
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
Department of Kampo Medicines, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
Clin Exp Pharmacol Physiol. 2017 Sep;44(9):924-931. doi: 10.1111/1440-1681.12797.
Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in haemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of haemodialysis patients. The median (range) of MP IC values against the proliferation of patients PBMCs was 7.04 (2.30-500.00) ng/mL. In contrast, the median (range) of MP IC values against the proliferation of healthy PBMCs was 4.44 (3.19-5.08) ng/mL. The median (range) of TET IC values against the proliferation of patients PBMCs was 1.61 (1.04-4.79) μmol/L. Lower concentrations of TET (0.3-300 nmol/L) were able to decrease the IC values of MP and thus potentiate the MP immunosuppressive effect on patient PBMCs. The median (range) of MP IC values in combination with 0.3, 3, 30, and 300 nmol/L TET were 0.92 (0.49-8.39), 2.10 (0.45-20.00), 0.35 (0.092-1.05), and 0.14 (0.05-6.78) ng/mL, respectively. TET potentiates the MP immunosuppressive pharmacodynamics and thus, it was possible to use the combination of MP and TET to attenuate MP side effects. There were significant correlations between the IC values of TET and stimulation indices (P=0.04, r=.58), the IC values of TET and the haemodialysis periods (P=0.04, r=.57), or the IC values of MP combined with 0.3 nmol/L TET and C-reactive protein concentrations (P=0.04, r=.64), respectively.
免疫抑制疗法用于预防急性排斥反应偶尔会引起严重的不良反应，因此开发针对肾移植受者的新治疗方法很重要。本研究通过使用从血液透析患者全血中分离出的外周血单个核细胞（PBMC），在体外评估了汉防己甲素（TET）和/或甲泼尼龙（MP）对血液透析患者的免疫抑制药效学。MP抑制患者PBMC增殖的IC值中位数（范围）为7.04（2.30 - 500.00）ng/mL。相比之下，MP抑制健康PBMC增殖的IC值中位数（范围）为4.44（3.19 - 5.08）ng/mL。TET抑制患者PBMC增殖的IC值中位数（范围）为1.61（1.04 - 4.79）μmol/L。较低浓度的TET（0.3 - 300 nmol/L）能够降低MP的IC值，从而增强MP对患者PBMC的免疫抑制作用。MP与0.3、3、30和300 nmol/L TET联合时的IC值中位数（范围）分别为0.92（0.49 - 8.39）、2.10（0.45 - 20.00）、0.35（0.092 - 1.05）和0.14（0.05 - 6.78）ng/mL。TET增强了MP的免疫抑制药效学作用，因此，有可能使用MP和TET的组合来减轻MP的副作用。TET的IC值与刺激指数之间（P = 0.04，r = 0.58）、TET的IC值与血液透析时间之间（P = 0.04，r = 0.57）、或MP与0.3 nmol/L TET联合时的IC值与C反应蛋白浓度之间（P = 0.04，r = 0.64）分别存在显著相关性。
