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Objective@#To investigate the effects of modified acidic fibroblast growth factor (MaFGF) mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction (UTMD) on left ventricular systolic function in early diabetes mellitus(DM) rats.@*Methods@#The nanoliposomes containing MaFGF(MaFGF-nlip) were prepared by reverse phase evaporation method. Among 60 male Sprague Dawley (SD) rats, 50 rats were randomly selected and were induced to be DM models by streptozotocin(STZ) through intraperitoneal injecting, the other 10 rats as control group. Then DM rats were randomly divided into 4 groups: DM model group, MaFGF solution group, MaFGF-nlip group and MaFGF-nlip+ UTMD group. After the successful induction of DM model, the intervention was performed twice a week.After 12 weeks of intervention, all rats underwent conventional echocardiography and velocity vector imaging (VVI). Left ventricular ejection fraction (LVEF) and left ventricular fraction shortening(LVFS) were measured by conventional echocardiography. The mean peak systolic radial velocity (Vs), radial strain (Sr) and radial strain rate (SRr) of six walls at the papillary muscle level were measured in left ventricular short-axis view by VVI. At last, myocardial tissue of all rats were stained with Sirius red to evaluate myocardial interstitial fibrosis. The level of myocardial apoptosis was evaluated by TUNEL staining, and the changes of myocardial ultrastructure were observed by transmission electron microscopy.@*Results@#The prepared MaFGF-nlip were more rounded, evenly dispersed, and of good stability and high encapsulation efficiency. Twelve weeks later after intervention, LVEF, LVFS, Vs, Sr and SRr in the DM model group were significantly lower than those in the control group (all P<0.05). LVEF, LVFS, Vs, Sr and SRr in the MaFGF-nlip+ UTMD group were significantly higher than those of the DM model group and other intervention groups (all P<0.05). The results of Sirius red staining and Tunel staining showed that CVF and AI in the DM model group were significantly higher than those in the control group (all P<0.05). For MaFGF-nlip+ UTMD group, CVF and AI were significantly decreased compared with the DM model group and other intervention groups(all P<0.05). According to the results of transmission electron microscopy, compared with the DM model group, the improvement of myocardial ultrastructure was the most obvious in the MaFGF-nlip+ UTMD group.@*Conclusions@#MaFGF delivered by using nanoliposomes combined with UTMD can improve the left ventricular systolic function in diabetic rats by inhibiting the myocardium cardiac fibrosis and reducing the cardiomyocyte apoptosis.
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OBJECTIVE:To observe therapeutic efficacy and safety of chloramphenicol combined with recombinant human acidic fibroblast growth factor (rhaFGF) in the treatment of traumatic perforation of tympanic membrane (TPTM).METHODS:A total of 82 TPTM patients were randomly divided into observation group (41 cases) and control group (41 cases).On the basis of routine treatment,the patients in the control group were covered with cotton sheets infiltrated with 12.5％ Chloramphenicol injection,and 1 drop of 12.5％ Chloramphenicol injection,once a day,since 2nd day.Observation group was covered with cotton sheets infiltrated with 12.5％ chloramphenicol injection+rhaFGF for external use,and 1 drop of rhaFGF,once a day,since 2nd day.Cotton sheets were removed every 7 days in 2 groups.After 60 days of treatment,clinical efficacies,infection rate and reoperation were observed in 2 groups,and air conduction threshold,bone conduction threshold and the occurrence of ADR were also observed before and after treatment.RESULTS:The total response rate of observation group was 78.05％,which was higher than 60.98％ of control group (P＜0.05).The reoperation rate and the incidence of ADR in observation group were significantly lower than control group,with statistical significance (P＜0.05).There was no statistical significance in the infection rate between 2 groups (P＞ 0.05).After treatment,air conduction threshold of 2 groups were significantly lower than before treatment,with statistical significance (P＜0.05);but there was no statistical significance between 2 groups (P＞0.05).There was no statistical significance in bone conduction threshold between 2 groups (P＞0.05).CONCLUSIONS:Chloramphenicol combined with rhaFGF is effective and safe in the treatment of TPTM,and can significantly reduce the rate of reoperation.
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Objective To explore the mechanism of the protection of acidic fibroblast growth factor (aFGF) for hippocampal astrocytes from injury induced by gentamicin. Methods Hippocampal astrocytes were isolated from newborn (24 hours) Sprague-Dawley rats, puri-fied, and identified with glial fibrillary acidic protein (GFAP) immunofluorescence. The third generations were cultured for 3 days and divid-ed into 3 groups:control group was cultured routinely, injury group was cultured with 2.0 g/L gentamicin for 24 hours, and protection group was cultured with 4.25μg/L aFGF for 24 hours and then cultured with 2.0 g/L gentamicin for 24 hours. Western blotting was adopted to de-tect the expressions of P38, extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2. Results Hippocampal as-trocytes were culturated successfully with the purity above 95%. The ERK1 increased in the injury group compared with the control group (P0.05). Conclusion The mitogen-activated protein kinase signal pathway, especially P38 and ERK1, may associate with the protection of aFGF for hippocampal astrocytes from injury induced by gentamicin.
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Objective To observe the recombinant human acidic fibroblast growth factor (rh-aFGF) treatment of open fractures of the tibia and fibula efficacy and safety.Methods Seventy-two cases of open fractures of tibia and fibula patients were selected,all patients were given the C-arm X-ray machine to guide needle,debridement,the entire complex fractures,external fixa tion device postoperative were given anti-infection treatment.Treatment group were given rh-aFGF 1-5 soluble solvent cleaning wounds and skin grafts,suture given daily dressing (3-4 spray/cm2,6-8 times/d).The control group was not given medication,continuous treatment after 7-14 d assess wound healing,wound complications and infection.Results Treated the wounds healing time,healing time,the incidence of delayed fracture healing,skin graft survival area,walking function recovery time,edema score,pain score,the incidence of severe infection and late healing in treatment group were significantly better than those in control group:(27.2 ± 13.1) d vs.(34.7 ± 12.3) d,(55.4 ± 17.4) d vs.(62.2 ± 18.7) d,(99.2 ± 1.2) ％ vs.(92.6 ± 3.6) ％,(2.2 ± 0.4) scores vs.(3.8 ± 0.4) scores,(2.1 ± 0.4) vs.(3.7 ± 0.2) socres,5.6％ (2/36) vs.30.6％ (11/36),2.8％ (1/36) vs.19.4％ (7/36),there were statistical differences (P ＜ 0.05).rh-aFGF treatment of major adverse reactions were mild itching.Conclusion The recombinant human acidic fibroblast growth factor can accelerate wound healing and reduce post-operative complications,reducing infection.
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Objective:To study the promotion effect of recombinant human acidic fibroblast growth factor ( rh-aFGF) on wound healing in children with surgery or accident injury. Methods: Totally 206 cases of injured children were randomly divided into two groups, the treatment group was given rh-aFGF, and the control group was treated with basic fibroblast growth factor (bFGF). The ob-servation of wound healing, infection and fat liquefaction in the children was recorded in 7 days,and the modification of scar, pigmenta-tion and adverse reactions were observed in 6 months after the treatment. Results:After the 7-day treatment by rh-aFGF and bFGF, the healing rate respectively was 88. 4% and 74. 2%, and the residual wound area was (2. 2 ± 1. 1) cm2 and (3. 9 ± 2. 4) cm2,respec-tively. Six months after the treatment, the scar incidence rate of the treatment group and the control group was 27. 2% and 67. 5%, and the incidence of pigmentation was 30. 1% and 69. 9%, respectively. Conclusion:Rh-aFGF is more effective than bFGF in pro-moting wound healing in children with surgery or accident injury. It can effectively promote wound healing, shorten the healing time, and diminish the area of scar and pigmentation.
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Objective:To evaluate the efficacy and safety of recombinant human acidic fibroblast growth factor( rh-aFGF)and re-combinant human basic fibroblast growth factor( rh-bFGF)in the treatment of deep second degree burn. Methods:A multicenter,pro-spective,randomized and double-blind clinical trial was conducted. Totally 216 cases of deep second degree burn were selected from five research centers and given appropriate antibiotics and nutritional supplement therapy. The wound of 108 cases in the observation group were rinsing with rh-aFGF(one bottle / 5cm2)according to the wound area at the time of admission followed by rh-aFGF daily spraying,3-4 press/cm2 ,6-8 times a day. The 108 patients in the control group were treated with rh-bFGF with the same regimen as the observation group. After the 30-day follow-up,the wound healing was evaluated in the two groups. Results:The complete healing time,debridement time,complete healing rate in 12 days and 15 days in the observation group were all better than those in the control group(P<0. 05). After the 7-day treatment,the level of leukocyte and seepage score of the observation group were both lower than those of the control group(P<0. 01). The moderate rate showed significant difference between the two groups(P<0. 05). Conclu-sion:rh-aFGF shows better clinical efficacy than rh-bFGF in the treatment of deep second degree burn with the similar safety.
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Objective:To evaluate the promoting surgery incision healing effect of recombinant human acidic fibroblast growth fac-tor ( rh-aFGF) in the treatment of children with open fractures. Methods:A multicenter, randomized and controlled clinical trial was conducted to study the efficacy of rh-aFGF. Totally 120 cases of injured children (age<14y) were randomly divided into two groups, the treatment group (n=60) was given rh-aFGF washing during the operation and spraying after the operation, and the control group ( n=60) was treated with normal saline. Both groups were given traction, screw or Kirschner wire fixation. The healing time, healing status and delayed healing were observed and compared in the two groups. Results:Stage I healing rate, the complete healing time and delayed healing rate in the treatment group was 86. 6%, (20. 3 ± 5. 6)d and 3. 3%, respectively, while that in the control group was 56.7%, (23.4 ±6.2)d and 15.0%, respectively. The differences between the two groups were significant (P<0.05 or 0.01). Conclusion:Rh-aFGF can effectively promote wound healing and shorten the healing time. For all these positive aspects,rh-aFGF de-serves wider clinical application in postoperative rehabilitation after open fractures.
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Objective To evaluate the recent impact and long-term effects of recombinant human acidic fibroblast growth factor (rh-aFGF) of cesarean section on women's abdominal incision healing.Methods In 516 cases of cesarean section in women,randomly divided into placebo group (172 cases),spray group (172 cases) and flush group (172 cases).The placebo group received 0.9％ sodium chloride washing abdominal incision suture.The spray group incision suture direcdy after the administration of rh-aFGF spray,per square meter of 3-4 sprays,3-5 times/d.The flush group was given before 2 rh-aFGF dissolved in 10-20 ml of 0.9％ sodium chloride directly after washing the incision suture,then given spray treatment.The recent follow-up of 15 d observed maternal abdominal incision healing.Long term follow-up of 3 months to observe the incision scar formation.Results The abdominal incision heating time was (8.6 ±3.5) d,that was obviously shorter than that in spray group (10.4 ±3.7) d and placebo group (12.7 ± 4.9) d (P ＜ 0.05).The delay healing accounted for 4.2％ (7/166) in flush group,significantly lower than that in placebo group (34/168,20.2％) and spray group (16/165,9.7％) (P＜ 0.05).There was no significant difference in the incidence of fat liquefaction,postoperative infection among three groups (P ＞ 0.05).Flush group exudation,abdominal wall adhesions was lower than placebo group and spray group [2.4％(4/166) vs.10.1％(17/168),5.5％(9/165),3.6％(6/166) vs.17.3％(29/168),9.7％(16/165)](P＜0.05).Long term follow-up,flush group scar area than spray group reduced by 13.5％,than placebo group reduced by 27.2％.Conclusions A recent rh-aFGF can reduce the cesarean section abdominal incision healing time and reduce abdominal wall adhesions and exudation;rh-aFGF the best dosage is intraoperative irrigation treatment spray combined with postoperative.
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Objective To study the healing effect of recombinant human acidic fibroblast growth factor(rhaFGF) expressed in E.coli on dermal chronic ulcers in diabetic rats.Methods Ten male Wistar rats were used to set up diabetic dermal chronic ulcers models.The wounds were sprinkled with rhaFGF and physiological saline,respectively.The wound area,wound cavity volume and healing time were recorded,granulation tissue growth and epithelization in wound were observed,and wound healing status was evaluated.Results Compared with control group,the wound area and wound volume at different day in rhaFGF group were significantly diminuted(P
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Objective To investigate the feasibility of recombinant adeno-associated virus encoding secrected forms of human acidic fibroblast growth factor transfecting endothelial progenitor cells.Methods sp-haFGF was obtained through combining signal peptide sequence of FGF-4 with native aFGF gene by PCR.sp-haFGF was cloned into AAV vector plasmid pAAV-IRES-hrGFP.Recombinant AAV encoding sp-haFGF was packaged through co-transfecting HEK293 cells with plasmid sp-haFGF-pAAV-IRES-hrGFP,pAAV-RC and pHelper.Ex vivo cultured EPCs were infected with concentrated rAAV.Expression of green fluorescent protein(GFP) in infected EPC was observed by fluorescence microscope and expression of sp-haFGF in EPCs was verified by RT-PCR and western blot analysis.Results Recombinant AAV encoding sp-haFGF was obtained.After EPCs being infected with rAAV,green fluorescence was found in about 20～30% EPCs,gene of(560 bp) was generated from EPCs by RT-PCR method,and(sp-haFGF) protein was detected in infected cells.Conclusion EPC was efficiently infected by rAAV encoding(sp-haFGF) and(haFGF) was expressed by EPCs,which establishes a basis for therapeutic angiogenesis by transgenic EPCs transplantation.
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Acidic fibroblast growth factor is an important proteins which may affect the growth of several cell types. As a specific mitogen, acidic fibroblast growth factor is identified to be correlated with many physiological and pathological mechanism. In this paper we review the progress in the study on the structure and function of acidic fibroblast growth factor. Some problems about its application are also discussed.
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Objective:To study the clinical application potential of aFGF and try to produce aFGF as gene engineering medicine.Methods:The complete encoding cDNA of human aFGF was isolated from human lung fibroblast with RT PCR.Recombinant human aFGF was expressed in secretory pichia expression system and purified with heparin sepharose chromatography.The activity of aFGF was detected in NIH3T3 proliferation assay,chick embryo chorioallantoic membrane assay(CAM) and wound healing assay.Results:The recombinant aFGF was expressed in large quantity(yield=12 mg/L) and was capable to promote proliferation of NIH3T3,angiogenesis and wound healing.Furthermore,those activities of aFGF could be agonized by recombinant FGFR extracellular domain.Conclusion:Recombinant human aFGF was expressed efficiently and possessed natural biological activities.
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AIM: To detect the inhibition effect of nitidine chloride on proliferation of human liver cell L-02 and human kidney cell 293 and the protective effect of acidic fibroblast growth factor(aFGF) on human liver cell L-02 and human kidney cell 293 damaged by nitidine chloride in vitro. METHODS: The MTT assay was used to assess the proliferation of human liver cell L-02 and human kidney cell 293 treated with nitidine chloride.The contents of SOD and MDA and LDH in cultural supernate were measured by ultraviolet spectrophotometry. RESULTS: Nitidine chloride inhibited the proliferation of human liver cell L-02 and human kidney cell 293 in a dose-dependent manner. CONCLUSION: Nitidine chloride has certain toxicity on human liver cell L-02 and human kidney cell 293.aFGF could protect human liver cell L-02 and human kidney cell 293 damaged by nitidine chloride.
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Aim To study the protective effect of modified acidic fibroblast growth factor (MaFGF) on renal ischemia/reperfusion injury of rats. Methods 32 Wistar rats were divided randomly into four groups;false operative control group, model control group, 8 ?g?kg-1 of MaFGF and 16 ?g?kg-1 of MaFGF groups with 8 animals in each group. Renal pathological changes were observed by light and electron microscope. Results As shown in pathology, compared with model control group, MaFGF group could significantly reduce edema, number of leukocytes appearing in the interstitium ,distention and destroy of renal tissues. Under EM, the ultrostructure(including microvilli, mitochondria and lysosomes etc.) of the tubular epithelial cells of MaFGF groups appeared lighter in injuries or even near normal. Conclusion MaFGF has a role in attenuation of renal damage or failure after ischemia-reperfusion injury of the kidney.
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Aim To investigate the protective effect of non-mitogenic human acidic fibroblast growth factor (nm-haFGF) on cerebral ischemia-reperfusion injury in mice. Methods Cerebral ischemia-reperfusion model was made by ligating bilateral carotid for 20 minutes in mice. These mice were randomly divided into model group( iv NS), two doses of nm-haFGF (iv 25、50 ?g?kg-1) groups, rhaFGF group(iv 50 ?g?kg-1) and sham- operated group. Step down test and Y-type electric maze were used to examine the effect of nm-haFGF on learning and memory of mice, then Even′s Blue(EB) level and NO level in brain of these mice were measured. Results The nm-haFGF significantly decreased numbers of errors of mice in 5 min in step down test and in Y-type electric maze test; EB and NO levels in brain of these mice were lower than those of model group respectively. Conclusion The nm-haFGF can protect cerebral ischemia-reperfusion injury in mice.