| Anemia affects the health of about one-third of the world’s population,it is a signal for many diseases that seriously affect people’s quality of life.Anemia is one of the common complications in patients with malignant tumors.Studies have indicated that chemotherapy drugs have the toxic side effect of bone marrow inhibition,and bone marrow is the main source of hematopoiesis and immune cells,and its bone marrow inhibition will lead to anemia.Clinical use of erythropoiesis-stimulating agents(ESA)for the treatment of anemia,but research shows that ESA can increase the morbidity and mortality of cancer patients with disease of heart head blood-vessel,etc.,its security still needed to be evaluated.Therefore,the research and development of new and more safe anti-anemia is still significance.The Polymerized porcine hemoglobin(pPolyHb)is a novel polymeric hemoglobin with oxygen-carrying and oxygen-releasing functions.An animal model of hemorrhagic anemia established during the research of pPolyHb as a proteinaceous drug for HBOCs.The amount of pPolyHb used in the process is large.In previous studies on the safety and efficacy of pPolyHb,it was found that pPolyHb could increase the red blood cell content in hemorrhagic anemia animals.In this paper,we first explore the application of pPolyHb in Chemotherapy-induced anemia(CIA)Whether pPolyHb can affect hematopoietic-related physiological state or function of CIA animals and regulate the level of Hb in CIA animals.For animal model establishment,Choosing the chemotherapeutic drugs CTX and CBP to explore the establishment of CIA model in mice.The anemia status of mice in CTX alone group and CTX+CBP combined group was compared.The specific methods of CIA were established by detecting the concentration of Hb in peripheral blood,the content of RBC and the content of hematopoietic related cytokines(EPO,GM-CSF,IL-6,IL-10,HIF-1a)in vivo.In this paper,the specific modeling protocol was adopted: CTX 100 mg/kg was intraperitoneally injected on the first three days,CTX 150 mg/kg was intraperitoneally injected on the fourth day,and CTX 200 mg/kg was intraperitoneally injected on the fifth day.pPolyHb was used in the anemia treatment of anemia mice after intervention and chemotherapy,respectively,to determine the therapeutic effect of pPolyHb on CIA mice.Intervention after chemotherapy: The mice were randomly divided into groups: 1)Control group;2)CTX natural recovery group;3)pPolyHb groups(0.3,1,10,50 mg/kg);4)Human erythropoietin(150,1000 U/kg)was positive Control group;5)albumin group(1,10,50 mg/kg);6)pig hemoglobin group(1,10,50 mg/kg).RBC and Hb concentrations in peripheral blood of mice in each group were measured after stopping injection of chemotherapeutic drugs for 3days.detection of EPO concentration in kidney tissue,GM-CSF in bone marrow cell suspension,Serum IL-6,IL-10,HIF-1α concentration of mice in each group by ELISA.The results showed that the doses of 1 mg/kg and 10 mg/kg in the pPolyHb group significantly increased the number of RBC and Hb in peripheral blood of mice with CIA.At the same time,it can increase the concentration of hematopoietic growth factors EPO and GM-CSF in mice with CIA,reduce the content of hematopoietic inhibitors(IL-6,IL-10)and balance the content of HIF-1alpha in vivo(P < 0.05).pPolyHb can improve the hematopoietic microenvironment in the body.Intervention with chemotherapy: pPolyHb was used to inject anemia in mice during chemotherapy,and CTX was injected intraperitoneally on day 1-10,and pPolyHb(1,10 mg/kg)and ESA on day 5-10(150 U/kg).By detecting the concentration of Hb,EPO,GM-CSF and IL-6,the experimental data showed that 1 mg/kg pPolyHb group could significantly increase the concentration of Hb in peripheral blood of anemia mice.The results of two experiments show that pPolyHb has a good therapeutic effect on mice with myelosuppressive anemia caused by chemotherapy drugs. |
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