Mechanism of angelica polysaccharide regulating mitochondrial apoptosis for improving bone marrow failure / 中国组织工程研究

ABSTRACT

BACKGROUND: Bone marrow failure is an important pathogenesis of aplastic anemia, and how to reverse bone marrow failure is an issue of concern. OBJECTIVE: To investigate the regulatory effect of angelica polysaccharide on the mitochondrial dysfunction in murine aplastic anemia. METHODS: Seventy-two ICR mice were randomly divided into control, model and treatment groups (n=24 per group). The mice in the latter two groups were used to establish the aplastic anemia models by60Co γ radiation, intraperitoneal injection of cyclophosphamide and intragastric administration of chloramphenicol, and were then given normal saline or 200 mg/kg angelica polysaccharide for 2 weeks, respectively. The control mice received no intervention. At 1, 7 and 14 days after modeling, peripheral blood cells and bone marrow mononuclear cells were counted, and mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy. After Lin- Sca-1+ c-Kit+ (LSK) cells were sorted from bone marrow cells, which were hematopoietic stem cells. The mitochondrial membrane potential, levels of reactive oxygen species, and the expression levels of Bcl 2, Bax, cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were detected. RESULTS AND CONCLUSION: Compared with the control group, in the model and treatment groups, there were obvious abnormalities in the peripheral blood routine test was the number of bone marrow mononuclear cells was decreased significantly, the mitochondrial number, mitochondrial membrane potential and Bcl 2/Bax ratio were decreased, and the level of reactive oxygen species and the expression of cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were significantly increased (P < 0.05). After angelica polysaccharide treatment, all above results were significantly improved as compared with the model group (P < 0.05). To conclude, angelica polysaccharide might improve hematopoietic function by up-regulating the mitochondrial membrane potential, increasing the mitochondrial membrane stability and reversing the levels of apoptotic factors.