Pharmacodynamics Studies On Leukopenia Induced By Cyclophosphamide Or ～(60)Co-γ Irradiation In Mice Administered Si-Wu-Ke-Li

Background and Purpose: Si-Wu-Ke-Li (SW) is derived from Si-Wu-Tang, a traditional Chinese formula which was first cited in "Tai Ping Hui Min He Ji Ju Fang". It consists of Rehmanniae Radix, Angelica Radix, Chuanxiong Rhizoma, and Paeoniae Radix. The study was carried out to observe both therapeutic and preventive effects of SW on leukopenia respectively. Methods: Cyclophosphamide (CY) and 60CO-γ ray were used to induce leukopenia, and the KM mice were administrated- by ig with different dose of SW in vivo. The peripheral blood cells, CFU-GM, CFU-S and nucleated cells in bone marrow were measured, and the DNA in bone marrow was inspected by UV-spectrophotometer. FuFangZaoFanWan was used as the positive control. Results: 1. CY induced a significant decrease in the number of WBC, BPC and Ret (P<0.05). In the therapeutic group, the number of WBC and Ret markedly increased in SW (10 g/kg) treated mice compared to CY-treated control (P<0.05). The number of BPC markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to CY-treated control (P<0.05). In the preventive group, the number of WBC markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to CY-treated control (P<0.05), and SW (10 g/kg) was better than the positive control (P<0.05). The number of BPC significantly increased in SW(5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to CY-treated control (P<0.05). The number of Ret markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to CY-treated control (P<0.05). 2. CY induced a significant decrease on the number of CFU-GM (P<0.05). In the therapeutic group, the number of CFU-GM significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) compared to CY-treated control (P<0.05). In the preventive group, the number of CFU-GM significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) compared to CY-treated control (P<0.05). 3. CY induced a significant decrease on the number of CFU-S (P<0.05). In the therapeutic group, the number of CFU-S significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) compared to CY-treated control (P<0.05). In the preventive group, the number of CFU-S significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) compared to CY-treated control (P<0.05), and SW (10 g/kg) was better than the positive control (P<0.05). 4. 60Co-γ irradiation induced a significant decrease in the number of WBC, BPC and Ret (P<0.05). In the therapeutic group, the number of WBC and Ret markedly increased in SW (10 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05). The number of BPC markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05). In the preventive group, the number of WBC markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05). The number of BPC markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05), and SW (10 g/kg) was better than the positive control (P<0.05). The number of Ret markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05), and SW (10 g/kg) was better than the positive control (P<0.05). 5. The number of endogenous CFU-S both in SW-treated mice and in the positive control significantly increased compared to 60Co-γ-irradiated control (P<0.05). In the therapeutic group, the number of endogenous CFU-S significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05). In the preventive group, the number of endogenous CFU-S significantly increased inSW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05). 6. 60Co-γ irradiation induced a significant decrease in the level of nucleated cells and DNA in bone marrow (P<0.05). In the therapeutic group, the number of nucleated cells and DNA in bone marrow significantly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05), and SW (10 g/kg) was better than the positive control (P<0.05). In the preventive group, the number of nucleated cells and DNA in bone marrow markedly increased in SW (5 g/kg, 10 g/kg, 20 g/kg) treated mice compared to 60Co-γ-irradiated control (P<0.05), and the augment of the DNA in bone marrow in SW (10 g/kg) treated mice was larger than the positive control (P<0.05). Conclusion: 1. SW by ig can significantly prevent decrease of leukocyte numbers in the peripheral blood and accelerate recovery from leucopenia induced by CY in mice. Both the number of CFU-GM and CFU-S increased in SW-treated mice. These findings indicate that SW has therapeutic and preventive effect on the CY-induced leukopenia. 2. SW by ig can significantly prevent decrease of leukocyte numbers in the peripheral blood and accelerate recovery from leucopenia induced by 60Co-γ irradiation in mice. The number of endogenous CFU-S, the level of nucleated cell and DNA in bone marrow increased in SW-treated mice. These findings indicate that SW has therapeutic and preventive effect on the 60Co-γ irradiation-induced leukopenia.