早期联合应用西地那非和脂肪间充质干细胞治疗可改善扩张型心肌病大鼠心功能。
Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy.
机构信息
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
出版信息
J Transl Med. 2010 Sep 26;8:88. doi: 10.1186/1479-5876-8-88.
BACKGROUND
We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC) and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM).
METHODS
Adult Lewis rats (n = 8 per group) were divided into group 1 (normal control), group 2 (saline-treated DCM rats), group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV) myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally), and group 5 (DCM rats with combined ADMSC-sildenafil). Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90.
RESULTS
The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p < 0.002). Conversely, oxidative index was highest in group 2, and also higher in groups 3 and 4 than in group 5 (p < 0.0003). The mRNA expressions of interleukin (IL)-10, Gro/IL-8, endothelial nitric oxide synthase, and Bcl-2 were lowest in group 2, and lower in groups 3 and 4 compared with group 5 (p < 0.0001). The mRNA expressions of matrix metalloproteinase-9, Bax, caspase 3, and stromal-cell derived factor-1α were highest in group 2, and higher in groups 3 and 4 than in group 5 (p < 0.0004). Apoptosis and fibrosis in LV myocardium were most prominent in group 2 and higher in groups 3 and 4 than in group 5, whereas angiogenesis and LV ejection fraction were lowest in group 2 and lower in groups 3 and 4 than in group 5 (p < 0.003).
CONCLUSION
Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.
背景
我们研究了早期联合自体脂肪间充质干细胞（ADMSC）和西地那非治疗是否能为扩张型心肌病（DCM）大鼠的心脏功能保存提供附加益处。
方法
成年 Lewis 大鼠（每组 8 只）分为 1 组（正常对照组）、2 组（盐水处理的 DCM 大鼠组）、3 组[2.0×106 个 ADMSC 植入 DCM 大鼠左心室（LV）心肌]、4 组（DCM 大鼠给予西地那非 30mg/kg/天，口服）和 5 组（DCM 大鼠联合 ADMSC-西地那非）。治疗于 DCM 诱导后 1 周开始，第 90 天处死大鼠。
结果
结果显示，线粒体连接蛋白 43 和细胞色素 C 的蛋白表达在 2 组中最低，而在 3 组和 4 组中低于 5 组（p<0.002）。相反，氧化指数在 2 组中最高，在 3 组和 4 组中也高于 5 组（p<0.0003）。白细胞介素（IL）-10、Gro/IL-8、内皮型一氧化氮合酶和 Bcl-2 的 mRNA 表达在 2 组中最低，在 3 组和 4 组中低于 5 组（p<0.0001）。基质金属蛋白酶-9、Bax、caspase 3 和基质细胞衍生因子-1α的 mRNA 表达在 2 组中最高，在 3 组和 4 组中高于 5 组（p<0.0004）。LV 心肌中的细胞凋亡和纤维化在 2 组中最为显著，在 3 组和 4 组中高于 5 组，而血管生成和 LV 射血分数在 2 组中最低，在 3 组和 4 组中低于 5 组（p<0.003）。
结论
早期联合 ADMSC/西地那非在保存 LV 功能方面优于单独治疗。
Zotero 插件