[Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound-targeted microbubble destruction technique on treating rats with experimental diabetic cardiomyopathy].

Objective The therapeutic effect of acid fibroblast growth factor 1(FGF1) on rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD). Methods The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.TypeⅠdiabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention followed by 2 weeks intervention stop, all rats underwent cardiac catheterization, and the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate of left ventricular pressure (LV±dp/dtmax) were measured.Then, the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining, TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and myocardial microvascular density (MVD). Results (1)Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency (84.3±2.8)% with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The hemodynamic evaluation showed that LVESP, LV + dp/dtmax and LV -dp/dtmax were all significantly higher, while LVEDP was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The CD31 immunohistochemical staining results showed that MVD was significantly lower in all DCM groups than in control group and was significantly higher in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic index was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). Conclusion FGF1 nano-liposomes combining with UTMD technique can significantly improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance myocardial MVD in DCM rats. Key words: Diabetic cardiomyopathies; Fibroblast growth factor1; Liposome; Ultrasound-targeted microbubble destruction technique