Protective Effect Of PPolyHb On Myelosuppression And Organ Damage Induced By Cyclophosphamide In Mice

According to the World Health Organization,cancer has become the second leading cause of death worldwide.Having Chemotherapy is one of the most preferred treatment to cancer.However,due to the lack of specific targets,chemotherapy drugs always kill tumor cells while damaging normal cells,accompanied by serious side effects^[1-3].In particular,bone marrow is vulnerable to cytotoxic damage.Myelosuppression is one of the serious and common side effects of cancer patients after chemotherapy^[4].As well as a common and life-threatening toxic reaction in the blood system.In addition,chemotherapy will also cause damage to normal tissues such as liver and kidney^[5].Currently,symptomatic treatment is mainly used to treat myelosuppression that is caused by chemotherapy,that is,peripheral blood cell reduction.The available intervention measures are reactive administration,namely after the injury of hematopoietic stem cells to prevent,can’t avoid doses of chemotherapy to reduce or delay,and potentially lower expectations of antitumor efficacy.Therefore,it is urgent to explore effective adjuvant strategies to prevent and reduce the side effects caused by chemotherapy^[6].Polymerized porcine hemoglobin（pPolyHb）is a new type of erythrocyte cell substitute.The research team found that pPolyHb can increase the hemoglobin content of anemic animals.Therefore,this article uses cyclophosphamide to establish a chemotherapy-induced myelosuppression model to explore whether pPolyHb has a protective effect on myelosuppression in mice.Methods:The chemotherapy drug cyclophosphamide（CTX）was used to explore the establishment of myelosuppression mouse model,and the optimal model was established based on the basic indicators of the survival state,survival rate and myelosuppression degree of the mice.To evaluate the effect of pPolyHb on bone marrow hematopoietic function by measuring the number of peripheral blood cells（WBC,RBC,HGB,PLT）and using hematoxylin-eosin staining for bone marrow histopathological analysis;Serum creatinine（CREA）and urea nitrogen（BUN）of mice were measured by blood biochemical analyzer,calculate the kidney index,analyze kidney pathology,and use Western Blotting（WB）technology to detect the expression levels of EPO and Nrf2 in kidney tissue.Explore the effect of pPolyHb on the kidney tissue of myelosuppressed mice;Serum alanine aminotransferase（ALT）and aspartate aminotransferase（AST）of mice were measured by blood biochemical analyzer.Liver index were calculated and pathological sections were made to explore the effect of pPolyHb on the liver tissues of mice.Results:Successfully established CTX high-dose myelosuppression model:CTX was injected intraperitoneally at 150mg/kg interval for 3 times;CTX medium-dose myelosuppression model:CTX100mg/kg was injected intraperitoneally 5 times and CTX50mg/kg was injected intraperitoneally for 3 times.pPolyHb（1/10/50mg/kg）after intervention:（1）The mice are active,with smooth hair,have a good diet,and improve the survival rate and body weight;（2）Increase peripheral blood cell count and improve bone marrow cell classification;（3）Reduce kidney index,avoid pathological damage of kidney tissue,and increase the protein expression of EPO and Nrf2 in kidney tissue;（4）The liver index and serum ALT and AST were decreased,and the pathological injury of liver was significantly alleviated.Conclusion:The results of this experiment show that pPolyHb can alleviate the myelosuppression caused by CTX in mice,and has a protective effect on kidney and liver in mice.Experimental data shows that the most effective pPolyHb dose（1/10/50mg/kg）is pPolyHb 50mg/kg.