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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.
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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.
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Aim To study the therapeutic effect of re-combinant human acidic fibroblast growth factor (rh-aFGF) carbomer 940 gel in the treatment of skin wound healing in type I diabetic rats. Methods Two types of skin trauma models, namely, full-thickness wound and scalded wound,were established in a model of type I diabetes mellitus using STZ-induced SD rats. The rats were divided into control group, vehicle group,90 AU rh-aFGF gel group and 270 AU rh-aFGF gel group in each skin wound models. The wound area and wound healing rate were used to evaluate the thera-peutic effect. The growth of fibroblasts, fibrocytes, collagen fibers and vessel capillaries in the wound was observed using HE staining and analysed by semi-quantitative score. Results The rh-aFGF carbomer gel significantly reduced the traumatic area as well as promoted the wound healing rate of the skin trauma model of SD rats of type I diabetes mellitus (P <0.05). HE staining showed that rh-aFGF carbomer gel significantly promoted the pathological score of fibro-blasts and collagen fibers(P<0.05). Conclusions rh-aFGF carbomer gel might play a protective role in micro-environment of wound and rh-aFGF, which could benefit for proliferation of fibroblasts and colla-gen, therefore promoting the healing process of skin wound in SD rats with type I diabetes mellitus, and it might be expected to be a new preparation for the treat-ment of chronic trauma in diabetes mellitus.
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Objepctive To explore the protective effect of modified recombinant human aFGF ( Mrh-aFGF) on the neurons in ventral tegmental area of rats with Parkinson’ s disease ( PD) . Methods The 54 SD rats were ramdomly divided into the control group,the model group and the treatment group,and there were 18 rats in each group. PD rats of the model group and the treatment group were induced by in-jecting 6-OHDA into the left substantia nigra compacta ( SNC) and ventral tegmental area ( VTA) to build the PD model. Rats in the treat-ment group were given Mrh-aFGF injection after lateral ventricle injection,and the behavioral changes of the rats were detected after apomor-phine injection. The morphologic features and pathological changes of neurons in the ventral tegmental area were observed by Nissl’ s staining and electronic microscope. Results Compared to the right VTA of PD rats,the number of neurons in left side ( the injured side) decreased significantly in the model group(P<0. 05). In the treatment group,the structure of left (the injured side) VTA was markedly improved and the number of neurons was increased one week,two weeks and four weeks after operation compared with the model group (P<0. 05). The neurons in the VTA of the model group were found to have karyopyknosis,endoplasmic reticulum,degranulation,mitochondria swelling,cristae disappear,pre-synaptic and post-synaptic membranes swelling,and synaptic cleft disappear. In the treatment group,the ultrastructure of the neurons in the VTA,such as nuclei,mitochondria,synaptic structure,kept well compared to the model group. Conclusion Mrh-aFGF could protect the neurons in the ventral tegmental area from the loss and improve the ultrastructure of the neurons of PD rats.
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Objective To investigate whether acid fibroblast growth factor (aFGF)can augument the number of endothelial progenitor cells ( EPCs), enhance their biological function and inhibit their apoptosis.Methods Mononuclear cells(MNCs) from human umbilical cord blood were isolated by Ficoll density gradient centrifugation,and cultured in vitro. After cultured six days, the attached cells were identified by flow cytometry and confocal laser scanning microscope. The cells were added with aFGF(2, 5, 10 μg/L) for 24 hours. Meanwhile, the attached cells in the group (aFGF 5 μg/L group)of the most obvious effects on EPCs was cultured for 6,12,24,48 h respectively ,accordingly, to explore the relationship between time and effect of aFGF 5 μg/L group. EPCs proliferation was assayed with CCK-8 kit assay. EPCs migration was assayed by modified Boyden chamber assay. EPCs adhesion assay was performed by replating cells on fibronectin-coated dishes,and then adherent cells were counted. Flow cytometry was uesd to detect cell apoptosis. Results Compared with control groop, aFGF can argument the number of EPCs and enhance the biological function of proliferation, migration, adhesion. In addition, aFGF can inhibit apoptosis of EPCs ( P ＜ 0. 05 ). The increase and inhibition ratio of apoptosis reached the maximum 24 h after administration of 5 μg/L( P ＜ 0.05 ). Conclusion The results of the present study define a novel mechanism of the action of aFGF: aFGF can augment the number of EPCs, enhance the functional activity and inhibit apoptosis in vitro.
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Objective To observe the changes of rotation behavior and tyrosine hydroxylase immunopositive neurons and investigate how Mrh-aFGF affects them in substantia nigra of Parkinson disease rats. Methods After building a rat model of Parkinson disease by injecting 6-OHDA into substantia nigra and ventral tegmental area,we used Mrh-aFGF to intervene rats by lateral ventricle injection to observe how behavior of rats induced by apomorphine and tyrosine hydroxylase immunopositive neurons in substantia nigra of rats changes,then quantitatively analyzed the change of tyrosine hydroxylase immunopositive neurons. Results Rotation behavior was not found in control group,otherwise,actuation time was shorted,time length was prolonged,and average velocity of rotation was accelerated in Parkinson disease rats(P