Experimental study on diabetic cardiomyopathy rats treated with NMFGF1 loaded PEG-modified nano-liposomes combined with ultrasound-targeted microbubble destruction technique / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the therapeutic effect and mechanism of non-mitogenic acid fibroblast growth factor 1( NMFGF1) on diabetic cardiomyopathy ( DCM) by using PEG-modified nano-liposomes combined with ultrasound-targeted microbubble destruction technique ( UTMD ) . Methods The NMFGF1 loaded PEG-modified nano-liposomes were prepared by a water-in-water emulsion method and their quality inspections were also investigated. Type 1 diabetes animal model was induced by intraperitoneal injection of streptozotocin ( 70 mg/kg) in male SD rats. The diabetic rats were raised twelve weeks after the diabetes model was established and DCM rats were selected by ultrasonic heart function examination. After two weeks of intervention, all rats were kept for another two weeks and then underwent transthoracic echocardiography examination. The rats were sacrificed and myocardial tissue was obtained to quantify myocardial collagen fraction ( CVF ) and cardiac myocyte apoptotic index by Sirius red staining and TUNEL staining. Results NMFGF1-loaded PEG-nano-liposomes showed a good morphology and 90.3％± 1.4％ NMFGF1 encapsulation efficiency. Compared with DCM group, NMFGF1group, and NMFGF1-PEG-nano-liposomes group, NMFGF1-loaded PEG-nano-liposome plus UTMD group showed increased left ventricular end diastolic diameter (LVIDd) [(7.36±0.42) vs (5.75±0.24), (6.64±0.27), (6.72±0.24)mm, all P<0.05]and leftventricularfractionshortening(LVFS) [(50±3) vs (33±2), (44±5), (43±3)mm, all P<0.05], and decreased left ventricular posterior wall thickness (LVPW) [(1.65±0.07) vs (1.89±0.08), (1.73±0.11), (1.73 ±0.07) mm, all P<0.05], with decreased CVF and apoptotic index(all P<0.05). Conclusion PEG-nano-liposomes combining with UTMD technique has a greater translational potential in the delivery of NMFGF1 for the treatment of DCM by attenuating oxidative stress-induced injury and may provide a promising strategy for treating diabetes cardiomyopathy.