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首页> 外文期刊>Critical care medicine >Bone marrow-derived mononuclear cell therapy alleviates left ventricular remodeling and improves heart function in rat-dilated cardiomyopathy.
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Bone marrow-derived mononuclear cell therapy alleviates left ventricular remodeling and improves heart function in rat-dilated cardiomyopathy.

机译:骨髓源性单核细胞疗法可减轻大鼠扩张型心肌病的左心室重构,并改善其心脏功能。

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摘要

OBJECTIVES: This study hypothesized that bone marrow-derived mononuclear cell (BMDMNC) therapy may improve cardiac function through preventing cell death, alleviating left ventricular (LV) remodeling, and enhancing angio-/vasculo-genesis, as well as preserving LV contractility in a rat model of dilated cardiomyopathy (DCM). DESIGN: A model of DCM in Sprague-Dawley rats was used to investigate the effects of BMDMNC therapy on inflammatory and oxidative response, energy depression, cellular apoptosis, expressions of protein kinase C-(PKC)-epsilon, and connexin43 protein (Cx43) in LV myocardium and heart function. SETTING: An animal model research laboratory at Kaohsiung Chang Gung Memorial Hospital. MEASUREMENTS: The rats were divided into group 1 (normal control, n = 8), group 2 (saline-treated DCM, n = 10), and group 3 (1.2 x 10 BMDMNC implanted into LV anterior wall on day 35 after DCM induction, n = 10). The DCM and normal control rats were killed on day 90 following DCM induction. RESULTS: The results demonstrated that Cx43 protein expression and messenger RNA expressions of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, endothelial nitric oxide synthase, and interleukin-10 were higher, whereas messenger RNA expressions of endothelin-1 and matrix metalloproteinase-9 were lower in groups 1 and 3 than in group 2 (all p < 0.05). Additionally, expressions of PKC-epsilon in plasma membrane and mitochondria and LV function were conserved in group 1 and improved in group 3, whereas cardiomyocyte apoptosis, mitochondrial oxidative stress, and fibrosis of LV myocardium were reduced in groups 1 and 3 than in group 2 (all p < 0.005). CONCLUSION: BMDMNC therapy in DCM significantly improves LV function by limiting cellular apoptosis, inflammatory and oxidative responses, and by up-regulating expressions of Cx43, PKC-epsilon, and energy transcription factors.
机译:目的:这项研究假设骨髓源性单核细胞(BMDMNC)治疗可通过预防细胞死亡,减轻左心室(LV)重塑,增强血管/血管生成以及保持左室收缩力来改善心脏功能。扩张型心肌病(DCM)的大鼠模型。设计:使用Sprague-Dawley大鼠的DCM模型研究BMDMNC治疗对炎症和氧化反应,能量抑制,细胞凋亡,蛋白激酶C-(PKC)-ε和连接蛋白43(Cx43)表达的影响在左心室心肌和心脏功能。地点:高雄长庚纪念医院的动物模型研究实验室。测量:将大鼠分为第1组(正常对照组,n = 8),第2组(经盐水处理的DCM,n = 10)和第3组(1.2 x 10 BMDMNC,在DCM诱导后第35天植入LV前壁) ,n = 10)。 DCM诱导后第90天杀死DCM和正常对照大鼠。结果:过氧化物酶体增殖物激活受体-γ共激活因子1α,内皮一氧化氮合酶和白介素10的Cx43蛋白表达和信使RNA表达较高,而内皮素-1和基质金属蛋白酶9的信使RNA表达较高。在第1和第3组中低于第2组(所有p <0.05)。此外,第1组和第3组中,质膜和线粒体PKC-ε的表达均保持保守,第3组有所改善,而第1、3组的心肌细胞凋亡,线粒体氧化应激和心肌纤维化较第2组有所降低。 (全部p <0.005)。结论:BMDMNC在DCM中的治疗可通过限制细胞凋亡,炎症和氧化反应以及上调Cx43,PKC-ε和能量转录因子的表达来显着改善LV功能。

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