自体骨髓干细胞动员治疗右心衰竭的实验研究

Treatment of right heart failure by mobilization of bone marrow stem cells in rats

目的:探讨粒细胞集落刺激因子(G-CSF)对野百合碱(MCT)诱导的大鼠右心衰竭(RHF)的治疗作用。方法:动物随机分为3组:正常对照组(CON组)、MCT组、MCT/G-CSF组,腹腔注射野百合碱诱导大鼠右心衰竭模型,采用G-CSF动员自体骨髓干细胞(BMSC),动员结束后采集外周血标本,流式细胞仪检测外周血单个核细胞中CD34+细胞含量。第4周分别对3组大鼠进行血流动力学检测,处死大鼠,取肝、心脏、肺组织行苏木精-伊红(H-E)染色。结果:①单个核细胞中CD34+细胞含量在MCT/G-CSF组明显高于MCT组、对照组,差异均具有统计学意义(P<0.01)。②实验第35 d,MCT组血流动力学指标明显高于对照组(P<0.05),RHF造模成功;MCT/G-CSF组则低于MCT组(P<0.05),说明G-CSF干预治疗取得疗效。③MCT组大鼠右心室、肝脏、肺组织出现RHF的病理学改变,MCT/G-CSF组的病理学改变部分逆转。结论:G-CSF能动员骨髓干细胞,部分逆转RHF的血流动力学和病理学改变、减缓RHF的发展,可以用于RHF的研究和治疗。

Objective ： To study the therapeutic effects of the mobilization of bone marrow stem cells on right heart failure （RHF） in rats. Methods： Thirty-nine male rats were randomly assigned to a normal control （ CON）, a monocrotaline （MCT） and a granulocyte-colony stimulating factor （G-CSF） group. RHF rat models were established by intraperitoneal injection of monocrotaline. The autologous bone marrow stem cells （BMSC） were mobilized with G-CSF, followed by collection of blood samples and detection of CD34 ^＋ cells by flow cytometry. Hemodynamic analysis was conducted at the fifth week, and then all the rats were sacrificed for hematoxylin-eosine staining of the heart, liver and lung tissue. Results： The content of peripheral blood CD34^＋ cells in the mononuclear cells was obviously higher in the G-CSF group than in the MCT and CON groups （P 〈 0.01 ）. On the 35th day after monocrotaline injection, hemodynamics indexes were markedly higher in the MCT than in the CON group （ P 〈 0. 05 ）, which meant the successful establishment of the RHF model, and lower in the G-CSF than in the MCT group （P 〈 0.05 ）, which suggested the effectiveness the G-CSF therapy. RHF-related pathologic changes were observed in the MCT group and partly reversed in the G-CSF group. Conclusion： G-CSF, capable of effectively mobilizing bone marrow stem cells, partly reversing RHF-related hemodynamic and pathologic changes, and slowing down the development of RHF, can be used in the treatment and study of RHF.