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.
ABSTRACT
Objective To investigate the advanced preventive effect of acid fibroblast growth factor (aFGF) on diabetic cardiomyopathy(DCM) by using heparin-modified nano-liposomes combined with ultrasoundtargeted microbubble destruction technique (UTMD).Methods aFGF-loaded nano-liposomes (aFGF-lips) were prepared by lyophilization technique.Type Ⅰ diabetes model was induced by intraperitoneal injection of streptozotocin (STZ,70 mg/kg) in male SD rats.Before and twelve weeks after intervention,all rats underwent the transthoracic echocardiography.The segmental mean peak systolic radial velocity (Vs),systolic circumferential strain (Sc),and systolic circumferential strain rate (SRc) were measured.The expression of aFGF in DCM rats was detected by western blot.The rats were sacrificed and myocardial tissue were stained with masson staining and Tunel staining to quantify myocardial collagen fraction(CVF) and cardiac myocyte apoptosis index(AI).Results aFGF-lips showed good morphology and aFGF encapsulation efficiency (89.4±1.2)％ with high stability.From the animal experiments,the echocardiographic indexes including Vs,Sc and SRc had significantly improvements over DM group (P＜0.05) and all other treatment group (P＜0.05).The Masson's trichrome staining demonstrated that CVF was significantly higher in DM group than in the control group and was significantly lower in the aFGF-loaded nano-liposome+UTMD group than other groups(all P＜0.05).The TUNEL results showed that AI was significantly higher in DM group than in the control group and was significantly lower in aFGF-loaded nano-liposome +UTMD group than other groups (all P＜0.05).Conclusion aFGF nano-liposome combining with UTMD technique can improve the functions and pathologies of the hearts in type 1 diabetes mellitus model,which might provide a novel technique for aFGF in DCM prevention.
ABSTRACT
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.