Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2 in gastrointestinal stromal tumors,leiomyomas and schwannomas

AIM： To investigate the role of vascular endothelial growth factor （VEGF/and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal strornal tumors （GISTs）. METHODS： Thirty-three GISTs, 15 leiomyomas and 6 schwannomas were examined by immunohistochemistry in this study. RESULTS： VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFRol and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Irnrnunohistochernical staining revealed that 26 GISTs （78.8%）, 9 leiornyornas （60.0%） and 3 schwannornas （50.0%/were positive for VEGF; 24 GISTs （72.7%/, 12 leiornyornas （80.0%） and 4 schwannornas （66.7%） were positive for VEGFR-1; 30 GISTs （90.9%/, 5 leiornyornas （33.3%/and 4 schwannornas （66.7%） were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas （P 〈 0.0001）. However, there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories. CONCLUSION： Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.

STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1

AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.

Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer

AIM:To characterize the implications of vascular endothelial growth factor(VEGF)-A in stromal cells and colorectal cancer and the expression of VEGF-A splice variants.METHODS:VEGF-A expression in tumor and stromal cells from 165 consecutive patients with colorectal cancer was examined by immunohistochemistry.The association between VEGF-A expression status and clinicopathological factors was investigated.Twenty freshfrozen samples were obtained for laser capture microdissection to analyze the splice variants of VEGF-A.RESULTS:VEGF-A was expressed in 53.9% and 42.4% of tumor and stromal cells,respectively.VEGF-A expression in tumor cells(t-VEGF-A) was associated with advanced clinical stage(stage 0,1/9;stage 1,2/16;stage 2,32/55;stage 3,38/66;stage 4,16/19,P < 0.0001).VEGF-A expression in stromal cells(s-VEGF-A) increased in the earlier clinical stage(stage 0,7/9;stage 1,6/16;stage 2,33/55;stage 3,22/66;stage 4,5/19;P = 0.004).Multivariate analyses for risk factors of recurrence showed that only s-VEGF-A expression was an independent risk factor for recurrence(relative risk 0.309,95% confidence interval 0.141-0.676,P = 0.0033).The five-year disease-free survival(DFS) rates of t-VEGF-A-positive and-negative cases were 51.4% and 62.9%,respectively.There was no significant difference in t-VEGF-A expression status.The five-year DFS rates of s-VEGF-A-positive and-negative cases were 73.8% and 39.9%,respectively.s-VEGFA-positive cases had significantly better survival than s-VEGF-A-negative cases(P = 0.0005).Splice variant analysis revealed that t-VEGF-A was mainly composed of VEGF165 and that s-VEGF-A included both VEGF165 and VEGF165b.In cases with no venous invasion(v0),the level of VEGF165b mRNA was significantly higher(v0 204.5 ± 122.7,v1 32.5 ± 36.7,v2 2.1 ± 1.7,P = 0.03).The microvessel density tended to be lower in cases with higher VEGF165b mRNA levels.CONCLUSION:s-VEGF-A appears be a good prognostic factor for colorectal cancer and includes VEGF165 and VEGF165b.

Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.

Neuronal differentiation effects of vascular endothelial factor on bone marrow stromal cells

BACKGROUND：Studies have demonstrated that bone marrow stromal cells （BMSCs） undergo neuronal differentiation under certain in vitro conditions.However,very few inducers of BMSC differentiation have been used in clinical application.The effects of vascular endothelial growth factor （VEGF） on in vitro neuronal differentiation of BMSCs remain poorly understood.OBJECTIVE：To investigate the effect of VEGF on neuronal differentiation of BMSCs in vitro,and to determine the best VEGF concentration for experimental induction.DESIGN,TIME AND SETTING：In vitro comparative study was performed at the Central Laboratory and Laboratory of Male Reproductive Medicine,Shenzhen Hospital of Peking University from October 2008 to August 2009.MATERIALS：Recombinant human VEGF165 was purchased from Peprotech Asia,Rehovot,Israel.Neuron-specific enolase （NSE） was purchased from Beijing Biosynthesis Biotechnology,China.METHODS：BMSCs were harvested from adult Sprague Dawley rats.The passaged cells were pre-induced with 10 ng/mL basic fibroblast growth factor for 24 hours,followed by differentiation induction with 0,5,10,and 20 ng/mL VEGF,respectively.MAIN OUTCOME MEASURES：Morphological changes in BMSCs prior to and following VEGF induction.Expression of NSE following induction was determined by immunocytochemistry.RESULTS：Shrunken,round cells,with a strong refraction and thin bipolar or multipolar primary and secondary branches were observed 3 days after induction with 5,10,and 20 ng/mL VEGF.However,these changes were not observed in the control group.At 10 days after induction,the number of NSE-positive cells was greatest in the 10 ng/mL VEGF-treated group （P〈 0.05）.The number of NSE-positive cells was least in the control group at 3 and 10 days post-induction （P〈 0.05）.Moreover,the number of NSE-positive cells was greater at 10 days compared with at 3 days after induction （P〈 0.05）.CONCLUSION：Of the VEGF concentrations tested,10 ng/mL induced the greatest number of neuronal-like cells in vitro from BMSCs.

Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-αcross-talk and cardioprotection

Background Vascular endothelial growth factor （VEGF） is one of major mediators of angiogenesis and survival factor in some tissue, however, its direct effects on cardiomyocytes remain poorly understood. Methods Rat neonatal ventricular myocytes were cultured in vitro. Akt phosphorylation was measured by Western blotting; the expression of stromal cell-derived factor α（SDF-1α）/CXCR4 axis was evaluated by real-time PCR and Western blotting. LY294002 and AMD3100 were used to interfere with the signaling of VEGF and SDF-1α/CXCR4 axis. Cardiac myocytes viability and injury were evaluated by trypan blue staining and lactate dehydrogenase （LDH） release. Results Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and FIk-1 dependent manner. VEGF attenuated H202 induced cardiac myocyte death. The phosphoinositol-3-kinase （PI3K） inhibitor, LY294002 and FIk-1 antibody abolished the beneficial effects of VEGF on H202 induced cell death. In the mean time SDF-1α-CXCR4 axis was up-regulated by VEGF through PI3K-Akt signaling and contributed to the protective effects of VEGF on H202 induced cell death. Interestingly, SDF-1α also promoted production of VEGF in cultured cardiac myocytes and LY294002 reversed the up-reguLation of VEGF induced by SDF-1α. Conclusion VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomvocvtes in vitro.

Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance

Background Esophageal carcinoma is a common kind of malignant tumor and about 90% of which is esophageal squamous cell carcinoma （ESCC）, and it has a high incidence in China. In recent years it has been argued that angiogenesis plays a key role in tumor growth and metastasis and it is a complex process influenced by many factors. This study was aimed to investigate the expression of PC cell-derived growth factor （PCDGF or progranulin） and vascular endothelial growth factor （VEGF） in ESCC tissue and their relationship with clinical pathological parameters of ESCC, clarify the role of PCDGF and VEGF in the angiogenesis of ESCC. Methods The expression of PCDGF and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry. The vascular endothelial cells in tumor tissues were labeled by antibody to CD105 for counting microvessel density （MVD）. Results The expression of PCDGF and VEGF in ESCC was significantly higher than that in normal mucosa. Expression correlated with the depth of tumor invasion, lymph node metastasis, and TNM （classification tumor, nodes, metastasis）. In ESCC, both the expression level of PCDGF and VEGF had a positive correlation with MVD and the expression of PCDGF had a significant correlation with the expression of VEGF. Conclusions These results show that both of PCDGF and VEGE have higher expression in ESCC, which indicate that they have a close relationship with angiogenesis. They may be involved in tumor growth, infiltration and metastasis through promoting tumor angiogenesis and may be an important index reflecting biological behavior and prognosis of ESCC.

Case Report: Pazopanib Treatment Response in a Patient with Metastatic Pleomorphic Dermal Sarcoma (Atypical Fibroxanthoma) with Circulating Tumor Cell-Derived Colonies as a Predictive Marker

Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunocompromised or previously irradiated patients. These are part of a spectrum of more aggressive fibro-histiocytic neoplasms. In the older literature, these have been termed aggressive or metastatic AFX, but currently these have been reclassified as pleomorphic dermal sarcomas (PDS) and systemic undifferentiated pleomorphic sarcoma (UPS, formerly malignant fibrohistiocytic sarcoma, MFH). We present the case of a 64-year old woman who developed a deeply invasive PDS on the vertex of her scalp invading to the galea, with in-transit scalp metastases. Very little information is available about optimal treatment of metastatic PDS lesions. The patient was initially treated with 2 cycles of epirubicin/ifosfamide chemotherapy, resulting in life-threatening complications. A pretreatment peripheral blood sample was sent for CTC-derived colony assay. This sample grew 8 colonies from 10 ml blood. The tumor failed to respond to epirubicin and ifosfamide, and after several months of hospitalization, a second peripheral blood CTC-derived colony assay grew >376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to function as a potential prognostic marker.

Transplantation of bone marrow stromal cells overexpressing humanvascular endothelial growth factor 165 enhances tissue repair in a ratmodel of radiation-induced injury

Background The multilineage differentiation potential ability of bone marrow stromal cells(BMSCs) showed great potential in tissue engineering, while vascular endothelial growth factor 165(VEGF165) promotes vasculogenesis and further promotes tissue regeneration. This study aimed to assess the ability of rat BMSCs expressing human VEGF A165(hVEGF165) to promote tissue repair in rat model of radiation-induced injury.Methods Rat BMSCs were isolated from the tibia. Plasmid DNA expressing hVEGF165 was stably transfected into BMSCs using liposomes. The right hindlimb muscle of 40 rats was irradiated using a 60 Co γ source(total dose 30 Gy). The animals were divided into four groups(n=10): not injected with BMSCs(control; group 1) or intramuscularly injected two times(once in 2 weeks) with pcDNATM3.1-transfected BMSCs(group 2), untransfected BMSCs(group 3), or hVEGF165-transfected BMSCs(group 4). Angiography was performed 1 week after the last injection of BMSCs; samples of the hindlimb muscle were subjected to transmission electron microscopy, ultrastructural analysis, reverse transcription-PCR(RT-PCR), Western blotting, and immunohistochemistry.Results Rat BMSCs with multipotent differentiation capacity were isolated. hVEGF165-transfected BMSCs overexpressed hVEGF165 mRNA and protein. Injection of BMSCs(groups 2–4) increased the average vessel number, density, diameter, and cross-sectional area; mRNA expression of the myogenic markers including myoblast determination protein, myogenin, and α-smooth muscle actin; and CD31 protein expression; and promoted the repair of blood vessels and myofibers after radiation-induced injury compared to group 1; each of these parameters and hVEGF165 mRNA or protein expression were markedly improved in rats injected with hVEGF165-transfected BMSCs compared to groups 2 and 3.Conclusions BMSCs expressing hVEGF165 enhanced the repair of radiation-induced tissue injury by promoting vasculogenesis and muscle fiber regeneration. BMSCs expressing hVEGF165 may have potential clinical applications.

Prognostic angiogenic markers(endoglin, VEGF, CD31) and tumor cell proliferation(Ki67) for gastrointestinal stromal tumors

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P < 0.001). The cut-off values of CD105(>1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis.Cases with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.

Angiogenic Potency of Bone Marrow Stromal Cells Improved by ex Vivo Hypoxia Prestimulation

Summary: To study the angiogenic potency of hypoxia-prestimulated bone marrow stromal cells (BMSCs) when transplanted into acute myocardial infarction models of rats. BMSCs were cultured under hypoxia condition for 24 h. Their expression of VEGF was investigated. The rat acute myocardial infarction models were made by coronary artery ligation and divided into 3 groups at random. In normoxia group, twice-passaged BMSCs were labeled with Bromodeoxyuridine (BrdU) and then implanted into the infarction regions and ischemic border of the recipients in 4 weeks. The rats in hypoxia group were implanted with hypoxia-prestimulated BMSCs. In control group, the model rats received only DMEM medium injection. Six-weeks after AMI, the infarction regions were examined to identify the angiogenesis and the expression of the VEGF. Our results showed that viable cells labeled with BrdU could be identified in the host hearts. The infarction regions in normoxia and hypoxia groups had a greater capillary density and increased VEGF expression than the regions in control group. The capillary density and VEGF expression in hypoxia group were higher than in normoxia group. It is concluded that the enhanced expression of VEGF in BMSCs could be induced by ex vivo hypoxia stimulation. BMSCs implantation promoted the angiogenesis in myocardial infarction tissue via supplying exogenic VEGF. Angiogenic potency of bone marrow stromal cells was improved by ex vivo hypoxia prestimulation though the enhanced VEGF expression.

胎儿生长受限患者胎盘组织中VEGFA、HIF-1α表达及临床意义

目的:探究胎儿生长受限(FGR)患者胎盘组织中血管内皮生长因子A(VEGFA)、缺氧诱导因子(HIF)-1α表达及临床意义。方法:选择2020年5月-2022年9月在本院确诊FGR并住院分娩的孕妇116例(FGR组)、分娩正常孕妇(新生儿正常)116例为对照组临床资料。qRT-PCR检测胎盘组织中VEGFA、HIF-1α的mRNA表达情况,免疫组化法检测VEGFA、HIF-1α的蛋白表达情况。Pearson相关性分析VEGFA与HIF-1α的相关性以及与FGR患者临床资料相关性;多因素logistic回归分析影响FGR发生的因素。结果:FGR组VEGFA蛋白阳性表达率(25.9%)低于对照组(64.7%),HIF-1α蛋白阳性表达率(67.2%)高于对照组(24.1%);FGR组胎盘组织中VEGFA mRNA表达水平(0.75±0.20)低于对照组(1.00±0.23),HIF-1α mRNA表达水平(1.26±0.25)高于对照组(1.01±0.19)(均P<0.05)。FGR患者胎盘组织中VEGFA mRNA与HIF-1α mRNA呈负相关(P<0.05)。FGR患者新生儿出生1 min Apgar评分、胎盘重量、胎盘体积、新生儿体重与VEGFA表达水平呈正相关,与HIF-1α表达水平呈负相关;HIF-1α升高为影响FGR发生的危险因素,VEGFA升高为保护因素(均P<0.05)。结论:FGR患者胎盘组织中VEGFA低表达、HIF-1α高表达,二者影响FGR的发生及新生儿出生质量。

脐血血管内皮生长因子水平及血气分析与新生儿视网膜出血相关性研究

目的:探讨脐血血管内皮生长因子(VEGF)水平及血气分析与新生儿视网膜出血(RH)的相关性。方法:选取产科分娩并且行新生儿眼底筛查的596例新生儿。统计新生儿眼底检查结果,根据是否伴有眼底出血分为RH组(230例)和正常对照组(366例),分析VEGF水平及血气分析与新生儿RH的关系。结果:596例新生儿中,RH发生率为38.59%(230/596)。两组患者在产妇年龄、产次、多胎、分娩方式、窒息、产钳助产、胎龄、VEGF、pH值、二氧化碳分压(PaCO_(2))、氧分压(PaO_(2))、碱剩余(BE)值比较,差异有统计学意义(均P<0.05);而在妊娠期糖尿病、妊娠期高血压、贫血、性别、出生体重比较,差异无统计学意义(均P>0.05)。阴道分娩、窒息、产钳助产、VEGF≥251.67pg/ml、pH值<7.32、PaCO_(2)≥52.53mmHg、PaO_(2)<24.37mmHg、BE值<-3.49mmol/L是影响新生儿RH的独立危险因素(均P<0.05)。结论:脐血VEGF水平及血气分析均与KH密切相关。

Expression of stromal cell-derived factor-1 in diabetic retinopathy

Background Neovascularization can cause vision loss in proliferative diabetic retinopathy （PDR） and may be affected by many factors. Stromal cell-derived factor-1 （SDF-1） is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor （VEGF） in the eyes with diabetic retinopathy. Methods The levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole （IMH）. Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry. Results The vitreous concentration of VEGF was significantly higher in eyes with PDR （（2143.7~1685.21） pg/ml） than in eyes with IMH （（142.42~72.83） pg/ml, P 〈0.001）. The vitreous level of SDF-1 was also significantly higher in eyes with PDR （（306.37~134.25） pg/ml） than in eyes with IMH （（86.91~55.05） pg/ml, P 〈0.001）. The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation （PRP） could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR （r=0.61, P 〈0.001）. The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes. Conclusions SDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.

VEGF-C、SDF-1、S1P对慢性心力衰竭患者发生主要不良心血管事件的预测价值

目的 探讨血管内皮生长因子C(VEGF-C)、基质细胞衍生因子-1(SDF-1)、1-磷酸鞘氨醇(S1P)对慢性心力衰竭(CHF)患者发生主要不良心血管事件(MACE)的预测价值。方法 选取2021年1月至2023年1月湛江中心人民医院收治的149例CHF患者为研究对象。根据是否发生MACE将患者分为MACE组(54例)和对照组(95例)。比较两组VEGF-C、SDF-1、S1P的水平,采用二元logistic回归分析进行多因素分析,并以ROC曲线评价预测CHF患者发生MACE的价值。结果 MACE组的VEGF-C和S1P水平低于对照组,而SDF-1水平高于对照组,差异有统计学意义(P <0.05)。VEGF-C和S1P均是CHF患者发生MACE的独立保护因素,而SDF-1是CHF患者发生MACE的独立危险因素(P <0.05)。VEGF-C和S1P单独检测的1-AUC分别为0.806和0.811,而SDF-1单独检测的AUC为0.844,VEGF-C、SDF-1、S1P三者联合的AUC为0.938(P <0.01)。结论 VEGF-C、SDF-1、S1P均是CHF患者发生MACE的影响因素,并在MACE的预测中均有一定的价值,其中3种指标联合检测的预测效能最高。

玻璃体腔注射雷珠单抗对增殖性糖尿病性视网膜病变患者视力及血清GAS6、SDF-1及VEGF的影响

目的 探讨增殖性糖尿病视网膜病变(PDR)给予玻璃体腔注射雷珠单抗药物对患者视力以及血清人生长停滞特异性蛋白(GAS6)、人基质细胞衍生因子1(SDF-1)、血管内皮细胞生长因子(VEGF)影响。方法 纳入2022年1月至12月收治的PDR患者82例,按照随机数字表法分为观察组和对照组,每组41例。对照组采用玻璃体切割术(PPV)治疗,观察组采用联合玻璃体切割术(PPV)术前经玻璃体腔注射雷珠单抗治疗。对比2组的治疗效果,2组患者术前与术后1周的视力以及眼压水平,2组患者术前与术后1周血清GAS6、SDF-1、VEGF水平变化,2组术后并发症发生情况。结果 观察组治疗总有效率为95.12%高于对照组的78.05%(P<0.05)。2组患者术后1周的眼压、血清GAS6、SDF-1、VEGF水平均较术前降低,且观察组术后1周的上述指标水平低于对照组(P<0.05)。2组术后1周视力较术前升高,且观察组视力水平高于对照组(P<0.05)。观察组患者术后并发症总发生率为4.88%低于对照组的24.39%(P<0.05)。结论 应用玻璃体腔注射雷珠单抗辅助PPV治疗PDR,效果满意,可显著提高患者视力,降低眼压,降低血清GAS6、SDF-1、VEGF水平,且术后并发症发生率低,值得推广。

多囊卵巢综合征患者血清血管内皮生长因子、内皮抑素水平及对卵巢间质血流的影响研究

目的探讨多囊卵巢综合征(PCOS)患者血清血管内皮生长因子(VEGF)、内皮抑素(ES)水平及对卵巢间质血流的影响。方法选取2014年7月—2015年9月在哈尔滨医科大学附属第二医院生殖中心就诊的PCOS患者96例作为PCOS组;选取同期因男方因素不孕而就诊于本院生殖中心的健康女性72例作为对照组。PCOS组根据稳态模型评价的胰岛素抵抗指数(HOMA-IR),分为PCOS胰岛素抵抗组(PCOS-IR组,n=47)和PCOS非胰岛素抵抗组(PCOS-NIR组,n=49)。采用酶联免疫吸附法测定所有受试者血清中的VEGF、ES水平。同时所有患者于卵泡早期应用经阴道彩色多普勒超声监测双侧卵巢间质血流,并计算出血流动力学参数:搏动指数(PI)和阻力指数(RI)。结果 PCOS-NIR、PCOS-IR组VEGF、ES水平高于对照组,PI、RI低于对照组,差异有统计学意义(P<0.05);PCOS-IR组VEGF、ES水平高于PCOS-NIR组,PI、RI低于PCOS-NIR组,差异有统计学意义(P<0.05)。PCOS患者VEGF水平与黄体生成素(LH)、睾酮(T)水平及LH/促卵泡刺激素(FSH)、HOMA-IR呈直线正相关(P<0.05),与PI、RI呈直线负相关(P<0.05);ES水平与LH、T水平及LH/FSH无直线相关性(P>0.05),而与PI、RI呈直线负相关(P<0.05),与HOMA-IR及VEGF水平呈直线正相关(P<0.05)。PCOS患者PI、RI与LH、T水平及LH/FSH、HOMA-IR均呈直线负相关(P<0.05)。多元线性回归分析结果显示,T、VEGF水平及HOMA-IR是PCOS患者PI的影响因素(P<0.05);LH、T、VEGF水平及HOMA-IR是PCOS患者RI的影响因素(P<0.05)。结论 VEGF、ES在PCOS患者血清中呈高表达,二者之间呈直线正相关且均与PCOS患者的HOMA-IR密切相关,同时VEGF的表达水平还与血清LH、T水平密切相关;VEGF与ES的表达失衡及HOMA-IR在PCOS卵巢间质血流异常增多中起主要作用。

VEGF、SDF-1在糖尿病视网膜血管病变发生、发展中的作用及机制

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质细胞衍生因子(stromal cell derived factor-1,SDF-1)在糖尿病视网膜血管病变中的作用机制。方法运用链脲佐菌素(STZ)注射及脂肪乳灌胃的方法构建糖尿病大鼠模型、糖尿病合并视网膜病变大鼠模型。随机分为对照组、糖尿病组、糖尿病合并视网膜病变12 w组、糖尿病合并视网膜病变24 w组,每组30只。对各组制模大鼠给予玻璃体内注射贝伐单抗进行干预,4 w后,处死动物提取视网膜组织。观察干预前后大鼠视网膜组织病理学变化,检测视网膜组织中VEGF、SDF-1基因和蛋白的表达。结果干预前,糖尿病组大鼠视网膜镜下表现与对照组大致相似,血管未见明显异常;糖尿病合并视网膜病变12 w组大鼠视网膜镜下可见各层细胞排列不整齐,偶见毛细血管内皮细胞突出内界膜;糖尿病合并视网膜病变24 w组大鼠视网膜镜下可见视网膜内界膜水肿明显,各层细胞排列明显不整齐,较多血管内皮细胞突出内界膜。干预后,对照组和糖尿病组大鼠视网膜组织镜下表现与干预前均无明显差异;糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组大鼠视网膜镜下均可见视网膜内界膜水肿明显减轻,毛细血管内皮细胞突出内界膜的情况明显得到改善。干预前,对照组、糖尿病组、糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组大鼠的视网膜组织中VEGF、SDF-1蛋白和基因的表达逐渐升高,4组间比较差异有统计学意义(F=8.56、7.46,P<0.05)。干预后4组大鼠的视网膜组织中VEGF、SDF-1蛋白和基因的表达均出现下降,以糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组下降更明显,4组间比较差异有统计学意义(F=9.06,7.26、P<0.05)。结论 VEGF、SDF-1参与了糖尿病视网膜血管病变的发生,阻断VEGF的表达能明显改善视网膜血管病变,且抑制VEGF表达可以下调SDF-1表达水平。

人参皂苷Rg3抑制急性白血病骨髓基质细胞HIF-1α及VEGF的表达及其机制探讨

目的探讨人参皂苷Rg3对急性白血病骨髓基质细胞HIF-1α及VEGF表达的作用及其可能的机制。方法培养正常人及急性白血病患者的骨髓基质细胞,MTT法检测人参皂苷Rg3对正常及急性白血病骨髓基质细胞增殖的抑制作用;RT-PCR检测人参皂苷Rg3处理前后急性白血病骨髓基质细胞HIF-1α及VEGF mRNA表达的变化;Western blot、免疫荧光检测人参皂苷Rg3处理前后急性白血病骨髓基质细胞HIF-1α、VEGF、p-Akt、p-ERK蛋白表达的变化。结果人参皂苷Rg3对骨髓基质细胞增殖抑制的最适作用时间为24h,最适作用浓度为40μg/ml;处理24h后,急性白血病骨髓基质细胞HIF-1α、VEGF mRNA表达及蛋白表达均明显减少(P<0.05);p-Akt及p-ERK蛋白表达亦较处理前明显减少(P<0.05)。结论人参皂苷Rg3可明显抑制急性白血病骨髓基质细胞HIF-1α、VEGF mRNA及蛋白水平的表达,同时可抑制与血管形成密切相关的MAPK、PI3K/Akt途径中Akt、ERK蛋白的磷酸化,提示人参皂苷Rg3可能通过阻断PI3K/Akt、MAPK信号途径抑制急性白血病骨髓的血管生成。

宫内缺氧对新生大鼠肺血管发育及肺血管内皮生长因子表达的影响

目的:观察宫内缺氧对新生大鼠常压、常氧生存状态下肺发育的影响,及对新生大鼠不同生存时间肺组织血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达变化,为探讨宫内缺氧患儿出生后的治疗方案提供实验依据。方法:建立宫内缺氧模型。实验分为空气对照组(对照组)和缺氧6 d组(缺氧组)。两组大鼠出生后均置于常压、常氧下饲养。分别于出生时、出生后第7天、第14天及第21天行肺血管形态检测,以免疫组织化学方法测定肺组织VEGF蛋白表达,实时(real time)-PCR测定肺组织VEGF mRNA表达及电子显微镜下观察肺血管内皮细胞变化。结果:随着日龄增长,缺氧组与对照组肺组织VEGF蛋白及mRNA表达均逐渐增加,缺氧组增长幅度减慢,增长曲线与对照组呈交叉现象。缺氧组与对照组大鼠出生后各时间点肺血管形态无明显差异。随着日龄增长,缺氧组内皮细胞增生较出生时减少;内皮细胞水肿明显,于第14天达高峰。结论:宫内缺氧新生大鼠肺VEGF表达增长幅度减慢,VEGF表达影响大鼠生后肺血管发育。