Santos Denis Pioli dos, Okoshi Katashi, Moreira Vanessa O, Seiva Fábio R F, Almeida Fernanda Losi Alves de, Padovani Carlos Roberto, Carvalho Robson Francisco, Okoshi Marina Politi, Cicogna Antônio Carlos, Castro Ana Valéria Barros, Pai-Silva Maeli Dal
Department of Morphology, Bioscience Institute, São Paulo State University, Botucatu, São Paulo, Brazil.
Growth Horm IGF Res. 2010 Apr;20(2):149-55. doi: 10.1016/j.ghir.2009.11.007. Epub 2010 Jan 8.
This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.
Male 90-100g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.
Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90+/-0.15; AAS 3.11+/-0.44; AAS-GH 2.94+/-0.47 g/kg; p<0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in AAS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.
In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure.
本研究评估生长激素（GH）对升主动脉狭窄（AAS）诱导的慢性心力衰竭大鼠骨骼肌形态及生肌调节因子（MRF）基因表达的影响。
选用体重90 - 100g的雄性Wistar大鼠进行开胸手术。通过在升主动脉放置不锈钢夹造成AAS。术后25周，大鼠每日皮下注射重组人生长激素（2mg/kg/天；AAS - GH组）或生理盐水（AAS组），持续14天。假手术动物作为对照。在治疗前后评估左心室（LV）功能。通过酶联免疫吸附测定法（ELISA）测量血清IGF - 1水平。麻醉后，比目鱼肌在液氮中冷冻。组织学切片分别用苏木精 - 伊红（HE）和苦味酸天狼星红染色，以计算肌纤维横截面积和胶原分数面积。通过逆转录聚合酶链反应（RT - PCR）分析MRF肌细胞生成素和肌源性分化抗原（MyoD）的表达。
各组间体重相似。AAS组和AAS - GH组均出现左心房扩张、左心室（LV）肥厚（LV质量指数：对照组1.90±0.15；AAS组3.11±0.44；AAS - GH组2.94±0.47g/kg；AAS组和AAS - GH组与对照组相比，p<0.05），且左心室后壁缩短速度降低。AAS组比目鱼肌纤维面积显著低于对照组和AAS - GH组；AAS - GH组与对照组之间无差异。AAS组胶原分数面积显著高于对照组；AAS - GH组与对照组和AAS组均无差异。与对照组相比，AAS组血清IGF - 1水平降低。AAS - GH组MyoD mRNA显著高于AAS组；AAS - GH组与对照组之间无差异。各组间肌细胞生成素mRNA水平相似。
在主动脉狭窄诱导的心力衰竭大鼠中，给予生长激素可使MyoD基因表达高于未治疗动物水平，维持肌肉营养并减轻间质纤维化。这些结果表明生长激素可能作为慢性心力衰竭辅助治疗具有潜在作用。
