王芳 栾晓 郭菲菲 孙向荣 韩晓华 公衍玲 刘虹 杨南 徐珞.Ghrelin 及其类似物 BIM-281 31、 BIM-281 25 对大鼠心衰模型肌肉生长抑
制素表达的影响[J].,2015,15(7):1233-1236 |
Ghrelin 及其类似物 BIM-281 31、 BIM-281 25 对大鼠心衰模型肌肉生长抑
制素表达的影响 |
Effect of Ghrelin and its Analogues, BIM-281 31 and BIM-281 25, on theExpression of Myostatin in a Rat Heart Failure Model |
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DOI: |
中文关键词: 肌肉 生长抑制素 Ghrelin 慢性心力衰竭 恶病质 肌肉萎缩 TNF-alpha |
英文关键词: Myostatin Ghrelin Chronic heart failure Cachexia Muscle wasting TNF-alpha |
基金项目:国家自 然科学基金项目( 31071014; 81 100260; 81 270460; 81300281); 山东省医药卫生科技发展计划项目( 2013WS0263);
青岛市科技局项目( 13-1-4-170-jch) |
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中文摘要: |
目的: 探讨 Ghrelin 及其类似物对大鼠慢性心力衰竭( CHF)模型肌肉 生长抑制素表达的影响。 方法: 实验组慢性心衰模型大
鼠分别注射两种不同 浓度的 ghrelin、ghrelin 类似物 BIM-28125 和 BIM-28131( 50 和 500 nmol/kg/ 天)而对照组则 注射等量的安慰
剂。 通过渗透微型泵给药, RT-PCR 和免疫印迹反应检测肌肉 生长抑制素的表达, 并且测定腓肠肌的重量以及血浆肿瘤坏死因 子
琢(TNF-琢)水平。 结果: 与 给予安慰剂的 CHF 大鼠相比,假手术组大鼠腓肠肌肌肉 重量显著增加;高浓度的 ghrelin 类似物BIM-281 25
和 BIM-28131 可使肌肉 生长抑制素 mRNA 的表达显著减少;两种浓度的 ghrelin、 BIM-28131 及低浓度的 BIM-28125 可使肌肉 生
长抑制素蛋白表达明显减少。 实验中使用 的药物均能够缓解 CHF 动物模型血浆 TNF-琢 水平的增加。 结论: 在 CHF 动物模型,应
用 ghrelin 及类似物 BIM-28125 和 BIM-28131 后,肌肉 生长抑制素的表达明显减少, 这可能是由于抗炎作用 导致的。 |
英文摘要: |
Objective:To investigate the influence ofghrelin or its analogues on myostatin in chronic heart failure (CHF).Methods:In an animal model of CHF, Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125 and BIM-281 31 in two
different concentrations (50 and 500 nmol/kg/day) compared to placebo. The compounds were delivered using osmotic mini pumps. The
expression of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and muscle mass of gastrocnemius muscle was
measured. The plasma levels of tumor necrosis factor alpha (TNF-琢) were measured.Results:The relative weight of the gastrocnemius
muscle of the sham-operated group was significantly increased compared to placebo-treated CHF rats. The application of ghrelin analogue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in comparison to placebo. Myostatin protein expression was significantly reduced in both concentrations of ghrelin and BIM-28131 and in the lower
concentration of BIM-28125. The increase of TNF-alpha plasma concentration in the CHF-animals could be abolished by all used sub--
stances.Conclusion:In an animal model of CHF, the expression of myostatin is significantly reduced in the skeletal muscle after appli
cation of ghrelin and most concentrations of its analogues BIM-281 25 and BIM-28131 possibly due to anti-inflammatory effects. |
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