Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats
Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats
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DOI：
10.1016/j.ijcard.2011.05.002
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发表时间：
2012-12-15
影响因子：
3.5
通讯作者：
Yip, Hon-Kan
中科院分区：
文献类型：
--
作者：
Sun, Cheuk-Kwan;Lin, Yu-Chun;Yip, Hon-Kan
背景资料：西地那非和骨髓来源的内皮祖细胞（BMDEPC）已被证明可以改善野百合碱（MCT）诱导的大鼠肺动脉高压（PAH）。我们测试西地那非和BMDEPC联合治疗是否对大鼠中MCT诱导的PAH产生额外的保护作用。将雄性Sprague-Dawley大鼠随机分配至仅接受生理盐水注射（第1组）、MCT（70 mg/kg）（第2组），MCT+自体BMDEPC（2.0 × 10（6）个细胞）移植（第3组）、MCT+西地那非（30 mg/kg/天）（第4组）和MCT + BMDEPC-西地那非组合（30 mg/kg/天）（第5组）。MCT给药后第3天，静脉注射BMDEPC和口服西地那非。血流动力学分析采用Labchart软件，而细胞和分子参数测定采用流式细胞术，实时PCR，TUNEL法，蛋白质印迹，免疫组化染色。到MCT处理后第35天，连接蛋白43、蛋白激酶C-Bcl-2、右心室（RV）内皮型一氧化氮合酶（eNOS）、肿瘤坏死因子-α（TNF-α）和半胱天冬酶3（caspase 3）表达增高与其他组比较，第2组的肺组织和肺组织中均存在显著性差异（均P <0.05）。
Background: Sildenafil and bone marrow-derived endothelial progenitor cells (BMDEPCs) have been shown to ameliorate monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in the rat. We test whether combined sildenafil and BMDEPC treatment exerts additional protection against MCT-induced PAH in rats.Methods: Male Sprague-Dawley rats were randomized to receive saline injection only (group 1), MCT (70 mg/kg) only (group 2), MCT plus autologous BMDEPC (2.0x10(6) cells) transplantation (group 3), MCT with sildenafil (30 mg/kg/day) (group 4), and MCT with combined BMDEPCs-sildenafil (30 mg/kg/day) (group 5). Intravenous BMDEPC and oral sildenafil were given on day 3 after MCT administration. Hemodynamics were analyzed using Labchart software, whereas cellular and molecular parameters were measured using flow cytometry, real-time PCR, TUNEL assay, Western blot, and immunohistochemical staining.Results: By day 35 following MCT treatment, lower expression of connexin43, protein kinase C-epsilon, Bcl-2, and endothelial nitric oxide synthase and higher expression of tumor necrosis factor-alpha and caspase 3 were found in right ventricle (RV) and lung in group 2 compared with other groups (all p