Hu Yanyan, Li Li, Shen Lin, Gao Haiqing, Yu Fei, Yin Wenbin, Liu Wei
Department of Geriatrics, Qilu Hospital of Shandong UniversityJinan 250012, China.
Shandong UniversityJinan 250012, China.
Am J Transl Res. 2017 Apr 15;9(4):1630-1640. eCollection 2017.
Till now, no functional studies for FGF-16 in diabetic heart have been reported. Therefore, this study aims to evaluate the potential function of FGF-16 in inhibiting adverse cardiac remodeling in post myocardial infarction (MI) of diabetic heart. We investigated the role of fibroblast growth factor-16 (FGF-16) in post-MI remodeling and role of cardio-protection in the diabetic infarct heart. Adult db/db diabetic mice were assigned to sham group, MI group and MI+FGF-16 group, respectively. MI group was induced by permanent coronary artery ligation, and the mice were subjected to 2D trans-thoracic echocardiography 2-4 weeks post-surgery. The results showed that the infiltration of monocytes, the associated pro-inflammatory cytokines were significantly increased, and the adverse cardiac remodeling and left ventricular dysfunction were observed in MI group. FGF-16 treatment protected against apoptosis, cardiac dysfunction and chamber dilatation post-MI, and decreased monocyte infiltration and cardiomyocyte hypertrophy/apoptosis. Meanwhile, the FGF-16 treatment also attenuated interstitial fibrosis and myocardial inflammation post-MI, increased M2 macrophage differentiation and associated anti-inflammatory cytokines, reduced adverse remodeling, and improved cardiac function. In conclusion, our results suggest that the heart appears to be a target of systemic and possibly locally generated FGF-16, which plays a therapeutic role in cardiac protection in the post-MI diabetic heart.
迄今为止，尚未有关于FGF-16在糖尿病性心脏病中功能研究的报道。因此，本研究旨在评估FGF-16在抑制糖尿病性心脏病心肌梗死后（MI）不良心脏重塑中的潜在功能。我们研究了成纤维细胞生长因子-16（FGF-16）在心肌梗死后重塑中的作用以及在糖尿病梗死心脏中的心脏保护作用。成年db/db糖尿病小鼠分别被分为假手术组、心肌梗死组和心肌梗死+FGF-16组。心肌梗死组通过永久性冠状动脉结扎诱导，术后2-4周对小鼠进行二维经胸超声心动图检查。结果显示，心肌梗死组单核细胞浸润及相关促炎细胞因子显著增加，出现了不良心脏重塑和左心室功能障碍。FGF-16治疗可预防心肌梗死后的细胞凋亡、心脏功能障碍和心室扩张，并减少单核细胞浸润以及心肌细胞肥大/凋亡。同时，FGF-16治疗还减轻了心肌梗死后的间质纤维化和心肌炎症，增加了M2巨噬细胞分化及相关抗炎细胞因子，减少了不良重塑，并改善了心脏功能。总之，我们的结果表明，心脏似乎是全身及可能局部产生的FGF-16的作用靶点，其在糖尿病性心脏病心肌梗死后的心脏保护中发挥治疗作用。
