Zhao Ying-Zheng, Zhang Ming, Tian Xin-Qiao, Zheng Lei, Lu Cui-Tao
College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang, People's Republic of China; Department of Ultrasonography, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang, People's Republic of China.
Int J Nanomedicine. 2016 Feb 18;11:675-86. doi: 10.2147/IJN.S99376. eCollection 2016.
Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/- UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes.
研究了负载碱性成纤维细胞生长因子(bFGF)的脂质体(bFGF-脂质体)联合超声靶向微泡破坏(UTMD)技术预防糖尿病性心肌病(DCM)。评估了心脏功能和心肌超微结构。采用末端脱氧核苷酸转移酶(TdT)介导的dUTP缺口末端标记(TUNEL)染色、免疫组织化学染色和蛋白质印迹分析来研究bFGF在DCM治疗中表达的信号通路。从Mason染色和TUNEL染色结果来看,bFGF-脂质体+UTMD组与糖尿病组以及其他接受bFGF或bFGF-脂质体治疗的组有显著差异。糖尿病组与其他bFGF治疗组的结果相似(心肌毛细血管密度、胶原体积分数和心肌细胞凋亡指数)。经胸超声心动图和血流动力学评估的指标也证实了相同的结论。这些结果证实,连续12周每周两次不同程度的bFGF治疗(游离bFGF或bFGF-脂质体+/-UTMD)可以不同程度地抑制包括舒张功能障碍、心肌纤维化和代谢紊乱在内的异常情况,其中bFGF-脂质体+UTMD组的改善最为明显。在所有组中,bFGF-脂质体与UTMD联合组的bFGF表达水平最高。bFGF激活了PI3K/AKT信号通路,导致心肌细胞凋亡减少和微血管密度增加。这种使用bFGF-脂质体和UTMD的策略是糖尿病DCM早期干预的一种潜在策略。