Time-course changes in VEGF expression and capillarity in the early stage of exercise training with Co treatment in rat skeletal muscles

AIM: Cobalt administration was reported to mimic hypoxia. This study was designed to examine the time-course changes in vascular endothelial growth factor (VEGF) expression and capillary geometry in skeletal muscles during endurance training with CoCl(2) administration in female Wistar rats. METHODS: Exercise training by running lasted for up to 10 days at 25 m min(-1) on a 20% gradient, 15-42 min day(-1). Rats in the Co(2+)-treated groups drank water containing 0.01% CoCl(2). Serial frozen sections were stained for alkaline phosphatase and dipeptidylpeptidase IV to identify capillary profiles and VEGF-A protein. RESULTS: In the soleus muscle, the density of VEGF-positive capillaries (VEGF-cap) was significantly increased after 6 and 10 days of the Co(2+) administration (by 27 and 65% respectively) while the capillary-to-fibre ratio (C : F) first increased after 10 days. The training with Co(2+) significantly increased VEGF-cap by 69, 44 and 60%, respectively, after 3, 6 and 10 days. The VEGF-cap was significantly increased after 6 and 10 days of training alone by 38 and 58%, respectively. In a similar extent, both training groups with and without Co(2+) showed a significant increase in the C : F ratio after 6 and 10 days. CONCLUSIONS: The present results suggest that activation of the cellular oxygen-sensing mechanism induced by Co(2+) administration slightly facilitates an expression of VEGF but does not facilitate exercise-induced microvascular remodelling in hind-leg muscles.     

Time‐course changes in arteriolar and venular portions of capillary in young treadmill‐trained rats

This study was designed to examine the time‐course changes in capillarity, especially the distribution of arteriolar and venular capillaries, in skeletal muscles during endurance training by running in young female Wistar rats. Exercise training by running started at the age of 5 weeks and lasted for 5 weeks at 25 m min^–1 on a 25% gradient, 10–60 min day^–1, 5 days per week. Morphological findings were obtained from the soleus (SOL) and deep portions of the medial gastrocnemius (GASd) muscles. In SOL, the training significantly increased the capillary‐to‐fibre ratio (C:F), total capillary density, and density of venular capillaries at Week 1. Significant increases in the C:F and total capillary density were also observed at Weeks 4 and 5. The capillary domain area (CDA) values for total capillary and arteriolar and venular capillaries were significantly decreased after 4 weeks of training. In GASd, the training significantly increased the C:F at Week 1 and from Week 3 onwards. It also significantly increased cross‐sectional area of all fibre types. Total capillary density and the CDA values showed no significant difference between control and training groups at all points of time. Significant increases in succinate dehydrogenase (SDH) activity were first noted after 2 weeks in GASd and after 3 weeks in SOL. These findings suggest that, in young growing rats, adaptive changes in the oxygen transport system occurred within 1 week after the onset of training mainly in highly oxidative muscles. The changes in arteriolar and venular capillary densities may help to clarify the growth pattern of the capillary network associated with endurance running training.     

Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer. Implications for the treatment with VEGF inhibitors

The vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis, and it is the target of innovative anti-cancer therapies. In colorectal carcinomas, differences in the VEGF expression have been found between the primary tumor and its metastases. We postulated that differences in the VEGF expression may also exist between liver and abdominal metastases from colon cancer. Consecutive colon cancer patients with liver or abdominal metastases were considered eligible for the study. Biopsies had to be performed before chemotherapy and the VEGF analysis were conducted through immunohistochemistry. The staining results were correlated to the metastatic pattern. The study population consisted of 41 patients with a metastatic site in the liver in 19 patients and the abdomen in 22 patients. A positive VEGF staining was found in 19 of the 41 metastatic samples (46%). Cases with positive VEGF expression were found more frequently in abdominal (15 out of 22 patients; 68%) than in liver metastases (4 out of 19 patients; 21%). Also, the degree of VEGF immunoreactivity was significantly higher in abdominal than in liver metastases. Evidence is supported that the VEGF expression may be different between colon cancer metastatic sites. The efficacy of anti-VEGF treatments may depend on the VEGF expression status, and this finding deserves further investigation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease

PurposeTo investigate the capacity of the peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) to produce vascular endothelial growth factor (VEGF), and to identify clinical associations of altered production of VEGF by PBMC in SSc. In addition, correlation with another pro-angiogenic cytokine, TNF-related weak inducer of apoptosis (TWEAK), was evaluated.MethodsPBMC were isolated from 25 patients with SSc and 17 healthy controls (HC). VEGF and TWEAK were measured in the supernatants of cultured PBMC using commercially available ELISA kits.ResultsPBMC from SSc patients spontaneously released significantly greater amounts of VEGF as compared with HC. Production of VEGF was comparable between patients with early SSc and those with longer disease duration, and in both SSc groups higher than in HC. Patients without active digital ulcers produced significantly greater amounts of VEGF as compared with HC, while there was no significant difference in the production of VEGF between SSc patients with active digital ulcers and HC. VEGF/TWEAK ratio was significantly higher in PBMC from SSc patients than in HC indicating that high production of VEGF is not paralleled by increased release of TWEAK in SSc.ConclusionsPBMC form SSc patients produce increased amounts of VEGF already in the early stage of disease. There is an imbalance in the profile of pro-angiogenic mediators produced by PBMC in SSc which might contribute to the pathogenesis of SSc. Further studies should address clinical significance of our findings.     

Altered ratios of pro‐ and anti‐angiogenic VEGF‐A variants and pericyte expression of DLL4 disrupt vascular maturation in infantile haemangioma

Infantile haemangioma (IH), the most common neoplasm in infants, is a slowly resolving vascular tumour. Vascular endothelial growth factor A (VEGF‐A), which consists of both the pro‐ and anti‐angiogenic variants, contributes to the pathogenesis of IH. However, the roles of different VEGF‐A variants in IH progression and its spontaneous involution is unknown. Using patient‐derived cells and surgical specimens, we showed that the relative level of VEGF‐A₁₆₅b was increased in the involuting phase of IH and the relative change in VEGF‐A isoforms may be dependent on endothelial differentiation of IH stem cells. VEGFR signalling regulated IH cell functions and VEGF‐A₁₆₅b inhibited cell proliferation and the angiogenic potential of IH endothelial cells in vitro and in vivo. The inhibition of angiogenesis by VEGF‐A₁₆₅b was associated with the extent of VEGF receptor 2 (VEGFR2) activation and degradation and Delta‐like ligand 4 (DLL4) expression. These results indicate that VEGF‐A variants can be regulated by cell differentiation and are involved in IH progression. We also demonstrated that DLL4 expression was not exclusive to the endothelium in IH but was also present in pericytes, where the expression of VEGFR2 is absent, suggesting that pericyte‐derived DLL4 may prevent sprouting during involution, independently of VEGFR2. Angiogenesis in IH therefore appears to be controlled by DLL4 within the endothelium in a VEGF‐A isoform‐dependent manner, and in perivascular cells in a VEGF‐independent manner. The contribution of VEGF‐A isoforms to disease progression also indicates that IH may be associated with altered splicing. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas

AIMS: Early gastric carcinomas have two characteristic growth types, superficial spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and lower p21(WAF1/CIP1) expression and submucosal low proliferative activity have been shown in the former, compared with the latter. In order to cast light on whether angiogenesis contributes to these growth patterns, the present immunohistochemical study was performed with cancer tissues. METHODS AND RESULTS: Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal invasive carcinoma cases were immunohistochemically compared. CD34 positivity, microvascular density (MVD), and expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX-2) were higher in cancer cells in both mucosal and submucosal layers in PEN than in SUP (P < 0.05). Submucosal MVD in PEN type was greater (P < 0.01) in cases with high than with low Ki67 labelling. Significant correlations were shown between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN type, but only a weak correlation between iNOS and COX-2 expression was evident with the SUP type. CONCLUSIONS: Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.     

环氧合酶-2抑制剂对大鼠骨关节炎模型软骨中血管内皮生长因子表达的影响

目的研究环氧合酶-2抑制剂(吲哚美辛)对大鼠骨关节炎模型关节软骨中血管内皮生长因子(VEGF)表达的影响。方法健康雄性wistar大鼠30只,随机均分为对照组、骨性关节炎组(OA组)和吲哚美辛处理组。利用膝关节注射4%的木瓜蛋白酶溶液的方法制作骨关节炎模型。采用关节炎评分法评定各组大鼠平均关节炎指数(MAI),免疫组化方法与Western blot方法检测关节软骨中VEGF蛋白的表达变化。结果 OA模型组随着造模的时间延长,关节出现了重度红肿现象,对照组关节无任何异常变化;与OA模型组比较,吲哚美辛组的关节炎症反应呈现消退现象。VEGF蛋白在对照组大鼠关节软骨仅有微量表达,而在术后8周OA组大鼠关节软骨表达则显著升高(P0.01);与OA组相比,吲哚美辛组大鼠关节软骨中VEGF蛋白表达显著降低(P0.01)。结论吲哚美辛对骨关节炎的抑制作用可能与下调VEGF蛋白的表达相关。     

癌组织中血管内皮生长因子表达及与微血管生成关系

目的　探讨血管内皮生长因子 (VEGF)在癌组织中的表达及其与癌组织血管生成、病理参数的关系。方法　采用S P免疫组织化学染色法检测 5 6例乳腺癌、5 9例食管癌及其癌旁正常组织各 10例的VEGF表达 ,并记数微血管密度。对每种癌组织各 10例进行VEGFmRNA原位杂交检测。结果　癌组织VEGF表达阳性率高于其正常组织 ,差异具有显著性 (P <0 0 5或P <0 0 1)。VEGF的表达与乳腺癌、食管癌的病理分级密切相关 (P <0 0 5 )。有淋巴结转移的病例 ,其VEGF表达率明显高于无淋巴结转移的病例 (P <0 0 5 )。而且随着VEGF表达的增强 ,癌组织内微血管密度明显增高 (P <0 0 1或P <0 0 5 )。结论　癌组织VEGF表达增强在肿瘤血管生成及生长、转移中起重要作用。     

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.     

Different adaptations of alpha‐actinin isoforms to exercise training in rat skeletal muscles

Aim: Alpha (α)‐actinins are located in the skeletal muscle Z‐line and form actin–actin cross‐links. Mammalian skeletal muscle has two isoforms: α‐actinin‐2 and α‐actinin‐3. However, the response of α‐actinin to exercise training is little understood. Therefore, the current study examined the effects of exercise training on the expression level of two α‐actinin isoforms in skeletal muscles. Methods: Twelve male Wistar rats were assigned randomly to a control (C; n = 6) or exercise training (T; n = 6) group. After T animals were trained on an animal treadmill for 9 weeks, α‐actinin‐2 and α‐actinin‐3 levels in the plantaris, white and red gastrocnemius muscles were analysed. In addition, changes in the myosin heavy chain (MyHC) composition were assessed, and muscle bioenergetic enzyme activities were measured. Results: Results show that exercise training increased α‐actinin‐2 expression levels in all muscles (P < 0.05). However, no significant difference was found in α‐actinin‐3 expression levels between C and T animals. Subsequent MyHC analyses of all muscle showed an MyHC shift with direction from IIb to IIa. Furthermore, enzymatic analysis revealed that exercise training improved enzyme activities related to aerobic metabolism. Conclusion: The results of this study demonstrate that exercise training alters the expression level of α‐actinin at the isoform level. Moreover, the increase in expression levels of α‐actinin‐2 is apparently related to alteration of skeletal muscle: its aerobic capacity is improved.     

血管内皮细胞生长因子及其受体2在慢性砷染毒大鼠睾丸中的表达及其意义*

目的：研究血管内皮细胞生长因子（ VEGF）及其受体2（ VEGFR2）在慢性砷中毒大鼠睾丸中的表达及意义。 方法：健康清洁级雄性SD大鼠随机分为高、中、低剂量砷染毒组和对照（ 蒸馏水）组,采用经口自由饮用方式 进行染毒,连续染毒6 个月。H-E 染色观察睾丸一般形态学变化,免疫荧光化学法对睾丸组织VEGF 和VEGFR2 的表达进行定位,采用实时荧光定量PCR法检测睾丸组织VEGF 和VEGFR2 的mRNA表达变化,流式细胞术观 察精子的凋亡率。结果：与对照组比较,中、高剂量砷组大鼠体质量明显降低,睾丸组织质量也明显降低,而低 剂量砷组大鼠体质量、睾丸质量、睾丸脏器系数差异无统计学意义。对照组睾丸结构正常,染砷组大鼠睾丸组织 上皮结构疏松,层次排列紊乱,层次逐渐减少,精原细胞出现空泡样改变,睾丸间质充血、渗出等,尤其中、高 剂量砷组有较明显的变化。与对照组比较,各染毒组VEGF 和VEGFR2 的mRNA表达水平均较低,砷染毒组大鼠 精子凋亡率较高,差异均有统计学意义。结论：慢性砷中毒时,VEGF 可能通过旁分泌- 自分泌的方式参与调控 大鼠睾丸的功能,VEGF 及其受体2 在砷中毒大鼠精子发生和发育过程中起重要作用。     

Triptolide Suppresses Alkali Burn‐Induced Corneal Angiogenesis Along with a Downregulation of VEGFA and VEGFC Expression

Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti‐inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical‐induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration, and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real‐time PCR and Western blot were used to determine the expression of vascular endothelial growth factor A (VEGFA) and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn‐induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose‐dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn‐induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. Anat Rec, 300:1348–1355, 2017. © 2017 Wiley Periodicals, Inc.     

The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

The role of high‐mobility group box protein 1 in collagen antibody‐induced arthritis is dependent on vascular endothelial growth factor

High‐mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti‐collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over‐expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up‐regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme‐linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)?1β, IL‐6 and tumour necrosis factor (TNF)‐α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL‐17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL‐17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA‐like model.     

miR‐155 overexpression is followed by downregulation of its target gene,NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the process of premetastatic niche formation is a crucial event according to modern concepts of tumour dissemination. The role of the present study was to investigate the expression levels of miR‐155, miR‐21, miR‐205 and miR‐let7b, as well as that of their target genes, in target organs of melanoma metastasis at the premetastatic stage. The expression levels of both the pro‐oncogenic miR‐155 and the tumour suppressive miR‐205 were found to be altered in the premetastatic liver of melanoma B16‐bearing mice. Bioinformatics analysis identified the target genes of miR‐155 to be nuclear factor, erythroid 2 like 2 (NFE2L2), secretogranin II, miR‐205, semaphorin 5A and vascular endothelial growth factor A (VEGFA). Among those, the redox status regulatory factor NFE2L2 was downregulated, which corresponded to increased levels of miR‐155. Due to the ability of pro‐oxidative events to initiate angiogenesis, VEGFA levels were evaluated in the premetastatic liver by immunohistochemistry, which revealed increased VEGFA expression in the central parts of the organ and diminished expression in the periphery. Taken together, these findings may support the concept of functional organ reorganization due to melanoma progression.     

Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I–II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0·018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0·0001) and VEGF-R2 ( p = 0·0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0·0001) and VEGF-R2 ( p = 0·04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0·0028) and VEGF-R2 ( p = 0·01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I–II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC. Copyright © 1999 John Wiley & Sons, Ltd.     

重组人促红细胞生成素对大鼠脊髓损伤后VEGF表达的影响

目的研究重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对急性脊髓损伤大鼠血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法参照Nystrom's压迫方法制作大鼠脊髓压迫损伤模型,成年健康Wistar大鼠72只,雌雄不限,按随机数字表法分为正常对照组8只、损伤组32只、重组人促红细胞生成素治疗组32只。免疫组化和Western blot检测各组大鼠VEGF的表达。结果免疫组化结果显示:损伤组VEGF阳性产物的平均光密度值(mean optic density,MOD)显著高于正常对照组(<0.01),rHuEPO治疗组与损伤组相比MOD值明显升高(<0.01)。Western blot结果显示:与正常对照组比较,损伤组VEGF积分光密度值(integrated density value,IDV)与内参照IDV的比值明显升高(<0.01),而rHuEPO治疗组则明显高于损伤组(<0.01)。结论 rHuEPO参与脊髓继发性损伤修复,可能与上调VEGF的表达相关。     

原发性中枢神经系统淋巴瘤VEGF、MVD与影像学对比研究

目的 :分析原发性中枢神经系统淋巴瘤 (PCNSL)的VEGF表达分布和测量其微血管密度 (MVD) ,旨在提高PCNSL早期诊断率和判断预后 ,同时为影像学提供理论依据。方法 :对 2 2例PCNSL临床 (包括影像学 )病理资料分析 ,同时行VEGF及CD34免疫组化标记 ,并测量MVD ,以 12例胶质瘤作为对照。结果 :2 2例PCNSL中单发者 17例 (占 77 2 7% ) ;多发者 4例 ,共有病灶 10处 ;1例为弥漫浸润型。肿瘤位于脑白质深部者 15例 (占 5 5 5 6 % )、脑表面及灰白质交界区者 8例、胼胝体者4例。CT示肿瘤为边界清楚的高密度结节或肿块。组织病理学示瘤细胞弥漫分布 ,瘤细胞大小较一致 ,胞质少 ,核大 ,可见瘤细胞围绕血管呈“袖套样”浸润。淋巴瘤MVD值 (2 1 8± 11 6 )与恶性胶质瘤组 (44 4± 16 8)的差异有非常显著性 (t =3 374 ,P <0 0 1)。VEGF表达无特异性 ,与对照组比较无统计学意义。结论 :病理学基础决定了影像学的特征。血管生成活性的不同 ,有助于PCNSL与恶性胶质瘤的鉴别 ,并对其预后的判断有一定帮助 ,VEGF可能是恶性肿瘤重要的促血管生成因子 ,但对于鉴别诊断无特异性。     

尿VEGF、ET检测对2型糖尿病患者早期肾脏微血管损伤的诊断价值

目的探讨尿血管内皮生长因子（VEGF）、内皮素（ET）对2型糖尿病患者早期肾脏微血管损伤的诊断价值。方法按尿微量蛋白排泄率把76例2型糖尿病患者分为无肾病、早期肾病、临床肾病3组。采用放射免疫法（RIA）和酶联免疫吸附试验（EHSA）测定尿VEGF、α1-微球蛋白（α1-MG）、β2-微球蛋白（β2-MG）、免疫球蛋白G（IgG）、ET水平。结果2型糖尿病患者尿VEGF、ET与对照组比较差异有统计学意义（t≥2．29，P〈0．01），且其水平随病情加重而明显升高；与α1-MG、β2-MG、IgG、Alb、糖化血红蛋白（HbAlc）呈正显著相关（r≥0．309）．而与空腹血糖（FBG）无明显相关（r≤0．06）。结论VEGF、ET参与糖尿病微血管病变的发生、发展；尿VEGF、ET是诊断2型糖尿病患者早期肾脏微血管损伤的敏感指标，对糖尿病肾病的早期诊断和肾功能损害程度的判断有一定的临床诊断价值。