Ghrelin及其类似物BIM-28131、BIM-28125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-28131 and BIM-28125, on the Expression of Myostatin in a Rat Heart Failure Model

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α(TNF-α)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-28125和BIM-28131可使肌肉生长抑制素m RNA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-α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。

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-28131 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-α） 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 ana- logue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in compari- son 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-ot plasma concentration in the CHF-animals could be abolished by all used sub-- stances. Conclusions： 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-28125 and BIM-28131 possibly due to anti-inflammatory effects.