摘要
目的通过给小鼠腹腔注射右旋糖酐铁,建立小鼠铁过载模型并观察铁过载对小鼠骨髓造血功能的影响。方法使用随机区组法将40只雄性C57BL/6小鼠随机分为对照组、低剂量铁剂组(质量浓度为12.5 mg/ml)、中剂量铁剂组(质量浓度为25 mg/ml)和高剂量铁剂组(质量浓度为50 mg/ml)。对照组小鼠腹腔注射生理盐水0.2 ml/次,低、中、高剂量铁剂组小鼠腹腔注射右旋糖酐铁0.2 ml/次,每3天注射1次,共注射6周。6周后观察小鼠状态及骨髓、肝脏、脾脏等脏器改变,分析骨髓单个核细胞(BMMNCs)可变铁池水平,并检测外周血象及BMMNCs数目和功能。结果小鼠肝脏、脾脏、骨髓均出现铁过载,骨髓铁过载主要存在于骨髓基质中,BMMNCs内可变铁池无改变;低、中、高剂量铁剂组小鼠骨髓细胞粒-单系集落形成单位数和对照组相比均显著下降(P<0.05);且中、高剂量铁剂组小鼠骨髓细胞红系集落形成单位数、混合系集落形成单位数和对照组相比也显著下降(P<0.05);BMMNCs计数无变化;低、中、高剂量铁剂组外周血白细胞、血小板、红细胞、血红蛋白和对照组相比,差异均无统计学意义,血小板数低剂量铁剂组(780.7±39.60)×109/L、中剂量铁剂组(676.2±21.43)×109/L、高剂量铁剂组(587.3±19.67)×109/L,和对照组(926.0±28.23)×109/L相比有轻度下降趋势,但差异无统计学意义(P>0.05)。结论通过腹腔注射右旋糖酐铁,成功建立了小鼠铁过载模型。进一步研究显示铁过载不但对肝脏、脾脏造成损害,而且可以损伤骨髓造血功能,但对正常骨髓功能的损伤未引起外周血象的改变。本模型为深入研究铁过载对骨髓造血功能的影响及作用机制提供了实验基础。
Objective To establish a mouse model of iron overload by intraperitoneal injection of iron dextran and investigate the impact of iron overload on bone marrow hematopoiesis. Methods A total of 40 C57BL/6 mice were divided into control group, low-dose iron group （12.5 mg/ml）, middle-dose iron group （25 mg/ml）, and high-dose iron group （50 mg/ml） . The control group received normal saline （0. 2 ml）, and the rest were injected with intraperitoneal iron dextran every three days for six weeks. Iron overload was con- firmed by observing the bone marrow, hepatic, and splenic iron deposits and the bone marrow labile iron pool. In addition, peripheral blood and bone marrow mononuclear cells were counted and the hematopoietic function was assessed. Results Iron deposits in bone marrow, liver, and spleen were markedly increased in the mouse mod- els. Bone marrow iron was deposited mostly within the matrix with no significant difference in expression of labile iron pool. Compared with control group, the ability of hematopoietic colony-forming in three interventional groups were decreased significantly （P 〈 0. 05 ） . Bone marrow mononuclear cells counts showed no significant differ- ence. The amounts of peripheral blood ceils （white blood ceils, red blood ceils, platelets, and hemoglobin） in different iron groups showed no significant difference among these groups; although the platelets were decreased slightly in low-dose iron group [ （780. 7±39.60）×10^9/L], middle dose iron group [ （676.2 ±21.43）×10^9/L], and high-dose iron group [ （587.3±19.67）×10^9/L] when compared with the control group [ （926.0± 28.23） ×10^9/L], there was no significant difference （P 〉 0.05） . Conclusions The iron-overloaded mouse model was successfully established by intraperitoneal administration of iron dextran. Iron overload can damage the hepatic, splenic, and bone marrow hematopoietic function, although no significant difference was observed in peripheral blood count.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2013年第5期547-552,共6页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(81041043)
天津市自然科学基金(13JCYBJC23400)~~
关键词
铁过载
动物模型
骨髓造血功能
iron overload
animal models
bone marrow hematopoietic functions
