Lima Aline R R, Pagan Luana U, Damatto Ricardo L, Cezar Marcelo D M, Bonomo Camila, Gomes Mariana J, Martinez Paula F, Guizoni Daniele M, Campos Dijon H S, Damatto Felipe C, Okoshi Katashi, Okoshi Marina P
Botucatu Medical School, Internal Medicine Departament, Sao Paulo State University, UNESP, Botucatu, Brazil.
School of Physical Therapy, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
Oncotarget. 2017 Aug 24;8(47):83009-83021. doi: 10.18632/oncotarget.20583. eCollection 2017 Oct 10.
Skeletal muscle wasting is often observed in heart failure (HF). The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is impaired in HF. In this study, we evaluated the effects of GH on soleus muscle and cardiac remodeling in rats with aortic stenosis (AS)-induced HF.
AS was created by placing a stainless-steel clip on the ascending aorta. After clinically detecting HF, GH (2 mg/kg/day) was subcutaneously injected for 14 days (AS-GH group). Results were compared with those from Sham and non-treated AS groups. Transthoracic echocardiogram was performed before and after treatment. Protein expression was evaluated by Western blot and satellite cells activation by immunofluorescence. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Student-Newman-Keuls.
Before treatment both AS groups presented a similar degree of cardiac injury. GH prevented body weight loss and attenuated systolic dysfunction. Soleus cross-sectional fiber areas were lower in both AS groups than Sham (Sham 3,556±447; AS 2,882±422; AS-GH 2,868±591 μm; p=0.016). GH increased IGF-1 serum concentration (Sham 938±83; AS 866±116; AS-GH 1167±166 ng/mL; p<0.0001) and IGF-1 muscle protein expression and activated PI3K protein. Neural cell adhesion molecule (NCAM) immunofluorescence was increased in both AS groups. Catabolism-related intracellular pathways did not differ between groups.
Short-term growth hormone attenuates left ventricular systolic dysfunction in rats with aortic stenosis-induced HF. Despite preserving body weight, increasing serum and muscular IGF-1 levels, and stimulating PI3K muscle expression, GH does not modulate soleus muscle trophism, satellite cells activation or intracellular pathways associated with muscle catabolism.
骨骼肌萎缩在心力衰竭（HF）中常被观察到。生长激素（GH）/胰岛素样生长因子-1（IGF-1）轴在HF中受损。在本研究中，我们评估了GH对主动脉狭窄（AS）诱导的HF大鼠比目鱼肌和心脏重塑的影响。
通过在升主动脉放置不锈钢夹来制造AS。在临床检测到HF后，皮下注射GH（2mg/kg/天），持续14天（AS-GH组）。将结果与假手术组和未治疗的AS组进行比较。在治疗前后进行经胸超声心动图检查。通过蛋白质印迹法评估蛋白质表达，并通过免疫荧光评估卫星细胞活化。统计分析：方差分析和Tukey检验或Kruskal-Wallis检验以及Student-Newman-Keuls检验。
治疗前，两个AS组的心脏损伤程度相似。GH可防止体重减轻并减轻收缩功能障碍。两个AS组的比目鱼肌横截面积均低于假手术组（假手术组3556±447；AS组2882±422；AS-GH组2868±591μm；p=0.016）。GH增加了血清IGF-1浓度（假手术组938±83；AS组866±116；AS-GH组1167±166ng/mL；p<0.0001）以及IGF-1肌肉蛋白表达，并激活了PI3K蛋白。两个AS组的神经细胞黏附分子（NCAM）免疫荧光均增加。各组之间与分解代谢相关的细胞内途径没有差异。
短期生长激素可减轻主动脉狭窄诱导的HF大鼠的左心室收缩功能障碍。尽管GH能维持体重、提高血清和肌肉IGF-1水平并刺激PI3K肌肉表达，但它并未调节比目鱼肌的营养状况、卫星细胞活化或与肌肉分解代谢相关的细胞内途径。
