重组人骨形成蛋白成熟肽4对急性放射损伤小鼠造血系统的修复作用

Reparation role of recombinant human bone morphogenetic protein-4 mature peptide on hematopoietic system of mice with acute radiation injury

目的探讨重组人骨形成蛋白成熟肽-4(rhBMP-4m)对^(60)Coγ射线照射引起的小鼠造血系统损伤的修复作用。方法 90只BALB/c小鼠随机分为正常对照组、模型组和rhBMP-4m治疗组,每组30只。模型组和rhBMP-4m治疗组小鼠接受^(60)Coγ射线照射,照射剂量7 Gy,全身照射200 s;正常对照组小鼠不接受照射。模型组小鼠每日腹腔注射生理盐水1.0 mL,rhBMP-4m治疗组小鼠每日腹腔注射rhBMP-4m 0.5 mg,连续治疗6 d。分别于照射后第1、3、5、7、9天检测小鼠外周血白细胞数、骨髓单个核细胞数、骨髓单个核细胞中CD34^+细胞比例;照射后第9天进行脾结节计数,并计算脾脏质量与体质量的比值(脾体比)。结果照射后第1天3组小鼠外周血白细胞计数比较差异均无统计学意义(P>0.05);照射后第3、5、7、9天模型组小鼠外周血白细胞计数低于正常对照组(P<0.01);照射后第3、5天rhBMP-4m治疗组小鼠外周血白细胞计数与模型组比较差异无统计学意义(P>0.05),照射后第7、9天rhBMP-4m治疗组小鼠外周血白细胞计数高于模型组(P<0.05)。模型组小鼠照射后各时间点骨髓单个核细胞计数均低于正常对照组(P<0.01)。照射后第1、3天rhBMP-4m治疗组小鼠骨髓单个核细胞计数与模型组比较差异无统计学意义(P>0.05),照射后第5、7、9天rhBMP-4m治疗组小鼠骨髓单个核细胞计数高于模型组(P<0.05)。模型组小鼠照射后各时间点的单个核细胞中CD34^+细胞百分率均低于正常对照组(P<0.01)。rhBMP-4m治疗组小鼠照射后第1、3天单个核细胞中CD34^+细胞百分率与模型组比较差异均无统计学意义(P>0.05),照射后第5、7、9天rhBMP-4m治疗组小鼠单个核细胞中CD34^+细胞的百分率高于模型组(P<0.05)。照射后第9天,模型组小鼠脾结节计数高于正常对照组,脾体比低于正常对照组(P<0.05);rhBMP-4m治疗组小鼠脾结节计数和脾体比高于模型组(P<0.01)。结论辐射可引起小鼠骨髓造血系统损伤,rhBMP-4m能够促进骨髓造血系统的重建。

Objective To explore the reparation role of recombinant human bone morphogenetic protein-4 mature peptide（ rhBMP-4 m） on hematopoietic system injury induced by irradiation in mice. Methods Ninety BALB/c mice were randomly divided into normal control group,model group and rhBMP-4 m treatment group,with 30 mice in each group. The mice in model group and rhBMP-4 m treatment group were irradiated by60 Co γ-ray（ 7. 5 Gy） for 200 s; while the mice in normal control group did not receive irradiation. After irradiation,the mice in model group were given physiological saline 1. 0 mL by peritoneal injection per day for 6 days; the mice in rhBMP-4 m treatment group were given rhBMP-4 m 0. 5 mg by peritoneal injection per day for 6 days. The peripheral white blood cell count and marrow mononuclear cells,the percent of CD34＋cells in marrow mononuclear cells of mice were detected on the first,third,fifth,seventh,ninth day after irradiation; the number of spleen nodus and the pleen weight/body weight ratio were detected at the ninth day after irradiation. Results There was no statistic difference in the number of peripheral white blood cells of mice among the three groups on the first day after irradiation（ P 0. 05）.The peripheral white blood cell count of mice in model group was significantly lower than that in the normal control group on the third,fifth,seventh,ninth day after irradiation（ P 0. 01）. There was no statistic difference in the number of peripheral white blood cells of mice between rhBMP-4 m treatment group and model group on the third,fifth day after irradiation（ P 0. 05）; the peripheral white blood cell count of mice in rhBMP-4 m treatment group was significantly higher than that in model group on the seventh,ninth day after irradiation（ P 0. 05）. The number of marrow mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation（ P 0. 05）. There was no statistic difference in the number of marrow mononuclear cells of mice between the rhBMP-4 m treatment group and model group on the first,third day after irradiation（ P 0. 05）; the number of marrow mononuclear cells of mice in rhBMP-4 m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation（ P 0. 05）. The proportion of CD34＋cells in mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation（ P 0. 01）. There was no statistic difference in the proportion of CD34＋cells in mononuclear cells of mice between the rhBMP-4 m treatment group and model group on the first,third day after irradiation（ P 0. 05）; the proportion of CD34＋cells in mononuclear cells of mice in rhBMP-4 m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation（ P 0. 05）. Compared with the normal control group,the number of spleen nodus was increased and the spleen weight/body weight ratio of mice was decreased in model group on the ninth day after irradiation（ P 0. 05）; the number of spleen nodus and the spleen weight/body weight ratio of mice in rhBMP-4 m treatment group were significantly higher than those in the model group on the ninth day after irradiation（ P 0. 01）. Conclusion rhBMP-4 m can accelerate the reconstruction of bone marrow hematopoietic system of mice with hematopoietic system injury induced by irradiation.