Clinical Observation of Recombinant Bovine Basic Fibroblast Growth Factor Eye Gel Combined with Tobramycin Dexamethasone Eye Drops in the Treatment of Dry Eye Syndrome in Patients after Cataract Surgery

Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.Methods:86 patients with DES after cataract surgery,admitted from November 2021 to November 2023,were randomly divided into groups.The observation group included 43 patients treated with rbFGF eye gel combined with TOB-Dex eye drops.The reference group included 43 patients treated with TOB-Dex eye drops alone.Multiple indicators,including total effective rate and clinical symptom scores,were compared between the two groups.Results:The total effective rate in the observation group was higher than in the reference group(P<0.05).Before treatment,there were no differences in clinical symptom scores,serum factors,or disease severity scores between the two groups(P>0.05).Three weeks after treatment,the observation group had lower clinical symptom scores,serum factors,and disease severity scores compared to the reference group(P<0.05).The adverse reaction rate in the observation group was lower than in the reference group(P<0.05).Conclusion:rbFGF eye gel combined with TOB-Dex eye drops can improve the clinical efficacy for patients with DES after cataract surgery,alleviate disease symptoms,reduce inflammatory responses,and have fewer adverse reactions.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Effect of charge at an amino acid of basic fibroblast growth factor on its mitogenic activity

The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF^(K119Q) and hbFGF^(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression system...

Effects of basic fibroblast growth factor on ischemic gut and liver injuries

AIMS To explore the possible effects of basic fibrob- last growth factor (bFGF) on ischemic gut and liver in- juries after trauma. METHODS Animal model of super mesenteric artery (SMA) occlusion was used in this study. Seventy-two Wistar rats were divided into three groups of 24 rats each. Each animal in group 1 (bFGF treated) was in- jected with 4 μg of bFGF in 0.15 ml of normal saline solution containing 0.1%(w/v) heparin through the jugular vein at the onset of reperfusion. Animals in group 2 (saline treated) received the same vehicle, but without bFGF. Group 3 (sham-operated) ani- mals were treated with the same operations,but without SMA occlusion. Liver function parameters, serum TNFα,bacterial examination and pathological study were used to evaluate the results. RESULTS In group 1,the amounts of ALT and AST and serum TNFα were reduced significantly at 6,24 and 48 hours as compared with group 2. Bacterial ex- amination showed that the bacterial translocation from gut to liver,spleen and MLN in group 1 was much lower than that in group 2. The pathological results support the concept of significant protecting effects of bFGF. CONCLUSIONS Venous administration of bFGF may help reduce gut and liver injuries after ischemia and reperfusion. Its mechanism of action may involve the mitogenic and non-mitogenic effects of bFGF.

Successful Management of Wound Dehiscence after Total Knee Arthroplasty by Topically Using Recombinant Basic Fibroblast Growth Factor

Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.

EXPRESSION AND SIGNIFICANCE OF BASIC FIBROBLAST GWOWTH FACTOR AND FIBROBLAST GROWTH FACTOR RECEPTOR-1 IN OVARIAN EPITHELIAL NEOPLASM

Objective To study the relevance of expression of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor 1 (FGFR 1) and carcinogenesis and progression of ovarian epithelial neoplasm. Methods Ten cases of normal ovarian tissues and 75 cases of ovarian epithelial neoplasm tissues were detected by immunohistochemical methods: S P for bFGF, FGFR 1,double immunohistochemistry Lab SA for Ki 67 antigen and bFGF. Results The expression level of bFGF, FGFR 1in ovarian epithelium and ovarian epithelial neoplasm showed a step wise increase in the following order:normal <benign <borderline <malignant; The expression level and intensity of bFGF and FGFR 1 were increased with the decrease of differentiation degree and increase of clinical stage in ovarian carcinoma; There was no statistical difference between the expression of bFGF, FGFR 1 in serous cystadenocarcinoma and that of mucinous cystadenocarcinoma; The expression of bFGF was correlated with that of FGFR 1 in neoplastic tissues; There were positive expression rates of bFGF and Ki 67 antigen in ovarian epithelial neoplasm. Conclusion As an important proliferative factor, bFGF plays an important role in carcinogenisis and progression of ovarian epithelial neoplasm.

Effect of Ligustrazine on Expressions of Basic Fibroblast Growth Factor and Its Receptor in Bone Marrow of Mice with Acute Radiation Injury

Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439

Effect of the implant composite of poly lactide-co-glycolide and bone mesenchymal stem cells modified by basic fibroblast growth factor on injured spinal cord in rats

Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and

Effect of electro-acupuncture on basic fibroblast growth factor protein and mRNA expression in hippocampal dentate gyrus of spleen deficiency rats

BACKGROUND： Spleen deficiency in traditional Chinese medicine refers to the functional disorder of spleen, pancreas, intestines, and nervous system in modern medicine. OBJECTIVE; To test whether electro-acupuncture could alter basic fibroblast growth factor （bFGF） protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo animal experiment was performed at the National LeveI-B Laboratory of Clinical Cell Molecule and Biology in Shenzhen Hospital of Traditional Chinese Medicine, between March and November in 2008. MATERIALS： Reserpine injection was produced by Guangdong Bangmin Pharmaceutical Co. Rhubarb extract granule preparation was produced by Guangdong Yifang Pharmaceutical. Huanqiu Brand sterile acupuncture pin was provided by Suzhou Acupuncture Supplies, China. Huatuo Brand electroacupuncture instrument （type SDZ-II） was purchased from Suzhou Medical Appliance Factory, China. METHODS： A total of 96 male Sprague Dawley rats were randomly assigned to control （n = 32） and induction （n = 64） groups. Spleen deficiency was induced via intraperitoneal injection of reserpine and intragastric administration of rhubarb. The successful models were randomized into two groups： model and electro-acupuncture, with 32 rats in each group. Electro-acupuncture was administered at Zusanfi （ST 36） and Sanyinjiao （SP 6） acupoints using a condensation wave and rarefaction （condensation wave 15 Hz） at a strength of 6-15 V for 20 minutes, once per day. The appearance of a slight shiver in the corresponding locus was taken as the standard. According to electro- acupuncture time points, each group was assigned to four subgroups at 7, 14, 28, and 49 days, respectively, with eight rats in each subgroup. Immunohistochemical staining, image analysis, and reverse-transcription polymerase chain reaction were performed at different time points. MAIN OUTCOME MEASURES： bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. RESULTS： After 7 days of electro-acupuncture therapy, bFGF protein and mRNA expression significantly increased compared with the model and control groups （P 〈 0.05）. After 14 days, bFGF protein and mRNA expression decreased until 28 days, where levels were then equal to the model group and greater than the control group （P 〈 0.05）. After 49 days, the above indices remained increased in the electro-acupuncture group compared to the model and control groups （P 〈 0.05）. CONCLUSION： Continuous electro-acupuncture maintained a high level of bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats.

Effect of basic fibroblast growth factor(bFGF) on the treatment of exposure of the orbital implants

Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.

The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

This study developed an animal model of surgically wounded submandibular glands （SMGs） and investigated the effects of collagen gel with basic fibroblast growth factor （bFGF） on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF （bFGF group） or without bFGF （control group）. In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day （AOD） 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, g-smooth muscle actin （αSMA）, CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin 19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration.

Effects of 530 nm monochromatic light on basic fibroblast growth factor and transforming growth factor-β1 expression in Müller cells

AIMTo expose rat retinal M&#x000fc;ller cells to 530 nm monochromatic light and investigate the influence of varying light illumination times on basic fibroblast growth factor (bFGF) and transforming growth factor-&#x003b2;1 (TGF-&#x003b2;1) expression.METHODSThree groups of rat retinal M&#x000fc;ller cells cultured in vitro under a 530 nm monochromatic light were divided into 6, 12 and 24h experimental groups, while cells incubated under dark conditions served as the control group. The bFGF and TGF-&#x003b2;1 mRNA expression, protein levels and fluorescence intensity of the M&#x000fc;ller cells were analyzed.RESULTSThe bFGF mRNA expression and protein levels were significantly upregulated in M&#x000fc;ller cells in all three experimental groups compared with the control group (P&#x0003c;0.05), while that of TGF-&#x003b2;1 was downregulated (P&#x0003c;0.05). Also, bFGF expression was positively correlated, but TGF-&#x003b2;1 expression was negatively correlated with illumination time. The largest changes for both cytokines were seen in the 24h group. The changes in bFGF and TGF-&#x003b2;1 fluorescence intensity were highest in the 24h group, and significant differences were observed among the experimental groups (P&#x0003c;0.05).CONCLUSIONThe expressions of bFGF and TGF-&#x003b2;1 changed in a time-dependent manner in M&#x000fc;ller cells exposed to 530 nm monochromatic light with 250 lx illumination intensity. M&#x000fc;ller cells might play a role in the development of myopia by increasing bFGF expression or decreasing TGF-&#x003b2;1 expression. Changes in cytokine expression in retinal M&#x000fc;ller cells may affect monochromatic light-induced myopia.

Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction

The present study established a mouse model of cerebral infarction by middle cerebral artery occlusion, and monitored the effect of 25 tJg/kg leukemia inhibitory factor and （or） basic fibroblast growth factor administration 2 hours after model establishment. Results showed that following administration, the number of endogenous neural stem cells in the infarct area significantly increased, malondialdehyde content in brain tissue homogenates significantly decreased, nitric oxide content, glutathione peroxidase and superoxide dismutase activity significantly elevated, and mouse motor function significantly improved as confirmed by the rotarod and bar grab tests. In particular, the effect of leukemia inhibitory factor in combination with basic fibroblast growth factor was the most significant. Results indicate that leukemia inhibitory factor and basic fibroblast growth factor can improve the microenvironment after cerebral infarction by altering free radical levels, improving the quantity of endogenous neural stem cells, and promoting neurological function of mice with cerebral infarction.

Noggin versus basic fibroblast growth factor on the differentiation of human embryonic stem cells

The difference between Noggin and basic fibroblast growth factor for the neural precursor differen- tiation from human embryonic stem cells has not been studied. In this study, 100 tJg/L Noggin or 20 IJg/L basic fibroblast growth factor in serum-free neural induction medium was used to differen- tiate human embryonic stem cells H14 into neural precursors using monolayer differentiation. Two weeks after induction, significantly higher numbers of neural rosettes formed in the Noggin-induced group than the basic fibroblast growth factor-induced group, as detected by phase contrast micro- scope. Immunofluorescence staining revealed expression levels of Nestin, [3-111 Tubulin and Sox-1 were higher in the induced cells and reverse-transcription PCR showed induced cells expressed Nestin, Sox-1 and Neurofilament mRNA. Protein and mRNA expression in the Noggin-induced group was increased compared with the basic fibroblast growth factor-induced group. Noggin has a greater effect than basic fibroblast growth factor on the induction of human embryonic stem cell differentiation into neural precursors by monolayer differentiation, as Noggin accelerates and in- creases the differentiation of neural precursors.

Expression of Basic Fibroblast Growth Factor in Rat Liver Fibrosis and Hepatic Stellate Cells

Summary:The expression of basic fibroblast growth factor (bFGF) in rat liver fibrosis and hepatic stellate cells (HSCs) and the relationship between the expression of bFGF and rat liver fibrogenesis were studied. Sixty male SD rats (230-260 g) were divided into 4 groups randomly (the 0 week group, 1 week group, 4 week group and 8 week group). Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride. The sections of rats' liver in each group were tested by Van-Gieson (V-G) staining and immunohistochemistry. The expression of bFGF mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). HSCs were isolated by the combined methods of collagenase IV perfusion and density gradient centrifugation. The expression of bFGF protein in cultured HSCs was detected by Western blot. Images of immunohistochemistry detection, agarose gel electrophoresis of RT-PCR and SDS-polyacrylamide gel electrophoresis of Western blot were analyzed semiquantitatively by image-analyzing system. The results were analyzed by statistics. The results showed that the fibers were gradually increased in the sections of rat liver with the prolongation of the model induction. At the end of the 8th weeks, liver fibrosis was formed. The expression of bFGF detected by immunohistochemistry showed a similar tendency of gradual increase. At the end of the 8th weeks, the bFGF expression could be observed in many regions in sections and the strongest expression was in interstitial cells including HSCs and some hepatocytes in regions around the portal area and central veins. Also there was moderate expression widely in extracellular matrix (ECM). In RT-PCR detection and Western blot detection of HSCs cultured in vitro, the similar tendency of gradual increase was evident either. It is suggested that bFGF is related with liver fibrosis of rats closely and may be a fibrogenesis factor of liver. bFGF possibly regulates liver fibrogenesis through regulating metabolism of extracellular matrix (ECM) by autocrine and paracrine stimulation.

Effect of basic fibroblast growth factor on cat corneal endothelial cell proliferation

AIM: To investigate the function of basic fibroblast growth factor (bFGF) on cat corneal endothelial cells proliferation. METHODS: Cat corneal endothelial cells were primarily cultured, stimulated with bFGF for different period, the proliferation of cells was assayed by modified tertrozalium salt (MTT) method, and the morphologic changes were observed with inverted phase contrast microscope and transmission electron microscope. RESULTS: At 1, 3 and 5 days after bFGF was added to cat corneal endothelial cells, the result of MTT in 490nm showed significant difference than that in control group, and the difference was most significant in 10ng/mL group. CONCLUSION: bFGF can promote proliferation of cat corneal endothelial cells. 10ng/mL is the relatively most effective dose.

THE EFFECT OF BASIC FIBROBLAST GROWTH FACTOR SLOW-RELEASE MICROCAPSULES ON ANGIOGENESIS IN INFARCTED RABBIT MYOCARDIUM

Objectives To observe the effect of basic fibroblast growth factor (bFGF) slow-release microcapsules on angiogenesis in infarcted myocardial regions. Methods.Myocardial infarction was induced in 24 New Zealand rabbits by ligating the root of left anterior descending coronary artery.Group Ⅰ(n=8) served as control, group Ⅱ(n=8) as a blank microcapsule group, group Ⅲ(n=8, each microcapsule contains 1μg bFGF) as micrpcapsule group.In group Ⅱ and Ⅲ, 5 blank microcapsules or bFGF slow-release microcapsules were implanted into myocardium underneath the epicardium between the left anterior descending coronary artery and left circumflex artery.Infarct size was evaluated by infarcted weight/left ventricle weight ratio and angiogenesis was evaluated by immunohistochemical examinations 5 weeks later. [WT5”BX] Results.As compared with group Ⅰ and Ⅱ, rabbits treated with bFGF slow-release microcapsules showed higher microvessel counts (group Ⅰ3775±450, group Ⅱ3837±498,vs.group Ⅲ 13550±481,P<0001) and less infarcted weight /left ventricle weight (group Ⅰ168%±04%,group Ⅱ167%±05%,vs.group Ⅲ 70%±02%,P<0001). Conclusions.Subepicardial administration of bFGF slow-release microcapsule in the infarcted rabbit model results in effective angiogenesis and reduction in infarct size.

Effects of basic fibroblast growth factor on beta-catenin protein and mRNA expression during the proliferation of endogenous neural stem cells following focal cerebral ischemia

BACKGROUND： The Wnt/β-catenin signaling pathway plays an important role in neural development. ,β-catenin is an important component of the Wnt/β-catenin signaling pathway. The Wnt signaling pathway has been shown to regulate the interaction of neural stem cells with the extracellular matrix. OBJECTIVE： To investigate the effects of basic fibroblast growth factor （bFGF） on β-catenin protein and mRNA expression, and on hippocampal neural stem cell proliferation in a rat model of cerebral ischemia/reperfusion. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiology experiment was performed in Shenyang Medical College between August 2006 and August 2008. MATERIALS： A total of 72 healthy male Wistar rats, aged 3 months, were used in this study. bFGF was provided by Beijing SL Pharmaceutical Co.,Ltd., China. METHODS： Rats were randomly divided into 3 groups： sham-operated, ischemia/reperfusion, and bFGF-treated （n = 24 per group）. Focal cerebral ischemia/reperfusion was induced in rats from the ischemia/reperfusion group and the bFGF-treated group by 2 hour right middle cerebral artery occlusion and 2 hour restoration of blood flow using the suture method. The ischemia/reperfusion and bFGF-treated groups were intraperitoneally administered 500 IU/mL of bFGF, or the same volume of physiological saline, once a day at postoperative days 1 3, and once every 3 days thereafter. Simultaneously, the sham-operated group underwent experimental procedures identical to the ischemia/reperfusion and bFGF-treated groups, with the exception of ischemia/reperfusion induction and drug administration. At 2 hours, 2, 6, 13, and 20 days after ischemiaJreperfusion induction, 50 mg/kg bromodeoxyuridine （BrdU） was administered to each group, twice daily, to label proliferating neural stem cells. MAIN OUTCOME MEASURES： The effects of bFGF on BrdU labeling, and ,8 -catenin mRNA and protein expression, in neural stem cells were examined by immunohistochemistry, Western blot, RT-PCR, and in situ hybridization techniques. RESULTS： In the sham-operated group, only a few BrdU-immunoreactive neural stem cells were found. In the ischemia/reperfusion group, BrdU-immunoreactive cells began to increase from 3 days after ischemia/reperfusion induction, reached a peak level at 7 days, and gradually reduced from 21 days. At 3, 7, 14, and 21 days after ischemia/reperfusion induction, the numbers of BrdU-immunoreactive cells were significantly greater in the bFGF-treated group than in the ischemia/reperfusion group. The sham-operated group exhibited slight expression of β-catenin and β-catenin mRNA. In the ischemia/reperfusion group, the expression of β-catenin and β-catenin mRNA gradually increased with reperfusion time, peaked at 14 days after reperfusion, and gradually decreased thereafter; by 21 days, the expression was markedly lower. Following bFGF injection, the expression of hippocampal BrdU, β-catenin, and β-catenin mRNA had apparently increased in each group. CONCLUSION： bFGF promotes neural stem cell proliferation, and the expression of β-catenin and β-catenin mRNA in the ischemic brain tissue. These findings indicate that bFGF promotion of neural stem cell proliferation may be mediated by Wnt/β-catenin signaling pathway.

Effects of basic fibroblast growth factor on hippocampal and parietal cortical neuronal cAMP-response element-binding protein expression in a rat model of focal cerebral ischemia/reperfusion

BACKGROUND： cAMP-response element binding protein （CREB） is a key modulator of various signaling pathways. CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE： To investigate the regulatory effects of basic fibroblast growth factor （bFGF） on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN, TIME AND SETTING： An immunohistochemical detection experiment was performed at the Department of Anatomy, Shenyang Medical College, between October 2006 and April 2008. MATERIALS： A total of 60 healthy, adult, Wistar rats were randomly divided into three groups： sham-operated （n =12）, ischemia/reperfusion （n = 24）, and bFGF-treated （n = 24）. Rabbit anti-rat CREB （1： 100） and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company, China. MetaMorph-evolution MP5.0-BX51 microscopy imaging system was provided by China Medical University, China. METHODS： Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion. Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF （500 IU/mL, 2 000 IU/kg） or an equal amount of physiological saline. Rats from the sham-operated group underwent a similar surgical procedure, without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES： After 48-hour reperfusion, hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry, and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS： The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons. In the ischemia/reperfusion group, the CREB expression was discrete and neurons were poorly arranged. The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group. The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group （P 〈 0.05）, and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group （P 〈 0.05）. CONCLUSION： bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.