Ginsenoside Rg1 improves bone marrow hematopoietic activity in cyclophosphamide-induced myelosuppression mice viaextramedullary hematopoiesis of the spleen

• Main Authors: Chen, Fei-Peng, 陳飛鵬
• Other Authors: Chang, Ko-Tung
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/29079254982363644173

碩士 === 國立屏東科技大學 === 生物科技系所 === 103 === Cyclophosphamide is a common chemical medicine for the treatment of cancer and immune diseases. The usage of cyclophosphamide causes bone marrow cytotoxicity resulting in bone marrow suppression in the patients and extramedullary hematopoiesis. Extramedullary hematopoiesis is the compensation happened underneath some pathological conditions, mainly due to bone marrow failure for growth and differentiation of stem and/or precursor cells. Extramedullary hematopoiesis occurs most often in the spleen and liver, occasionally appearing in the lymph nodes and other tissues. Xu et al found that treatment of ginsenoside Rg1 can improve hematopoietic stem and progenitor cells in cyclophosphamide-induced myelosuppressive mice. We therefore suspect that the recovery of bone marrow hematopoietic activity accompanies a relief of extramedullary hematopoiesis in the spleen. We followed clinical doses indication and administered cyclophosphamide (50 mg/kg) to mice for 4 days by intraperitoneal injection. Then we injected mice with ginsenosides Rg1 (15mg / kg) intraperitoneally for another 7 days. After that, mice were sacrificed and total bone marrow and splenocytes were analyzed by histology and flow cytometry. Our results showed that the weight of spleen in cyclophosphamide-induced mice reduced after Rg1 treatment. The number of hematopoietic stem and progenitor cells (Lin-, c-Kit +, Sca-1 + ; LSK) in the spleen were also decreased but not as a result of apoptosis. However, the proportion of splenic megakaryocytes was unchanged. These data manifested that treatment of ginsenosides Rg1 in cyclophosphamide-induced mice was able to alleviate extramedullary hematopoiesis. Meantime, the proliferative activity of c-Kit + stem and progenitor cells was also significantly increased in the spleen, but not in bone marrow. We also found an increased population of c-Kit + cells in the peripheral blood. Interestingly, when we treated Rg1 in cyclophosphamide-induced mice without the spleen, the effect of Rg1 on bone marrow was suppressed. The results demonstrated that extramedullary hematopoiesis in the spleen induced by cyclophosphamide confers the functionality of Rg1. Our findings also illustrate that treatment of Rg1 in cyclophosphamide-induced mice very likely changes the microenvironment of the spleen. Hence, Rg1 upregulates the proliferation and homing activity of c-Kit + stem and progenitor cells in the spleen that eventually leads to bone marrow hematopoietic improvement.