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目的:临床实践及动物模型中发现雄性心力衰竭个体的性激素水平降低,尤其血浆睾酮水平降低。本研究拟在构建右心衰竭大鼠模型的基础上,采用睾酮生理补充疗法改善心功能,并探讨雄激素心脏保护作用的可能机制。方法:43只SD健康雄鼠随机分为3组:右心衰组(RHF,n=15):野百合碱一次性腹腔注射6周构建右心衰竭大鼠模型;睾酮治疗组(TT,n=15):大鼠野百合碱注射后第3天开始睾酮生理性补充;对照组(CON,n=13):同期等量生理盐水替代,其余处理同前。每2周各组大鼠取外周血,分别化学发光法、酶联免疫吸附法测外周血浆睾酮、TNF-α水平,流式细胞术检测外周血CD34+细胞含量。于第6周各组存活大鼠行右心系统血流动力学测定,取心脏、肺脏、肝脏组织行常规病理及免疫组化检测。结果:RHF组各项指标显示大鼠右心衰竭模型造模成功,且血浆睾酮水平逐渐下降、TNF-α水平增加明显;TT组大鼠睾酮生理性补充治疗后心功能改善明显,但不能完全逆转,血浆睾酮水平较RHF组大鼠有所恢复,TNF-α减少有显著性差异;TT组大鼠、RHF组大鼠外周血CD34+细胞含量、免疫组化示右心室心肌细胞CD34+表达无明显差异。结论:睾酮生理补充能够改善右心衰竭雄性大鼠的心功能,可能通过抑制炎症因子TNF-α等的释放,而非通过自体动员骨髓干细胞的途径起作用。睾酮生理补充可以作为右心衰竭治疗的新辅助手段之一。
OBJECTIVE: In clinical practice and in animal models, it is found that the levels of sex hormones in individuals with congestive heart failure are reduced, especially in the plasma testosterone level. In this study, we intend to build a rat model of right heart failure, based on the use of testosterone physiotherapy to improve cardiac function, and to explore the possible mechanism of androgen cardioprotection. Methods: Forty-three healthy male SD rats were randomly divided into three groups: right heart failure group (RHF, n = 15): rats were induced by monocrotaline 6 weeks into the right heart failure model; = 15): Testosterone physiological supplementation started on the third day after injection of monocrotaline in rats. CON group (CON, n = 13): the same amount of saline was replaced at the same period, and the rest were the same as above. Peripheral blood was taken every 2 weeks, and the levels of peripheral plasma testosterone and TNF-α were detected by chemiluminescence and enzyme-linked immunosorbent assay. The levels of CD34 + cells in peripheral blood were measured by flow cytometry. At the 6th week, the rats in each group survived and the right ventricular system hemodynamics were measured. The heart, lung and liver tissues were examined by routine pathology and immunohistochemistry. Results: All indexes of RHF group showed successful model of right heart failure in rats, and the level of plasma testosterone gradually decreased and the level of TNF-α increased obviously. The cardiac function of TT group rats improved obviously after physiological supplementation, but not completely The level of CD34 + in peripheral blood of rats in TT group and RHF group was significantly lower than that in RHF group, while the level of CD34 + in RHF group was no significant difference . Conclusion: Physiological supplement of testosterone can improve heart function in right-heart failure male rats, which may be through the inhibition of the release of inflammatory cytokines such as TNF-α, but not by autologous mobilization of bone marrow stem cells. Physiological supplementation of testosterone can be used as a new adjunct to the treatment of right heart failure.