~(31)P-MRS无创量化肝细胞癌细胞代谢水平及其与血管生成的关系

目的 利用~(31)P-MRS对肝细胞癌(HCC)量化的代谢情况,探讨肿瘤血管生成及其成熟度对代谢的影响.方法 对经病理证实的肝细胞癌31例在手术前行~(31)P-MRS扫描,分析肿瘤和周围肝实质的细胞内pH值(pHi)、磷酸单脂(PME)、磷酸双脂(PDE)、无机磷(Pi)、γ-ATP、β-ATP、α-ATP、PME/ATP、Pi/ATP、PME/PDE、PME/Pi、PDE/Pi、PDE/ATP和低能磷酸盐(LEP)等.利用免疫组化技术检测肿瘤的VEGF、Flk-1表达情况及PCNA指数,利用病理图像自动分析系统统计微血管和成熟血管的数目、平均面积、总面积、周长、直径、异型指数、血管间距、表达部位、动脉数、静脉数、血管成熟指数和平均灌注分数等参数.利用HE染色计算细胞外间隙(ES)面积及细胞外血管外间隙(EES).将~(31)P-MRS技术测得的指标与血管参数进行对照分析.结果 HCC的pHi、PME/PDE以及Pi、β-ATP的峰下面积都高于肝脏(P＜0.05);PDE/ATP、PDE/Pi则相反(P＜0.05).Pi/ATP在VEGF阳性和阴性表达时差异有统计学意义(P=0.047,f=2.135),PDE/Pi在Flk-1阳性和阴性表达组也具统计学意义(P=0.001,t=2.13).pHi在CD34不同表达部位之间存在统计学意义(P=0.01,F=7.493).pHi与静脉数呈正相关(P=0.003,r=0.749);PME与EES负相关(P=0.029,r=-0.583);Pi与微血管总面积正相关(P=0,r=0.766);γ-ATP与动脉数目呈正相关(P=0.012,r=0.648).与β-ATP有关有ES、PI及微血管的直径、周长和平均面积等(P＜0.05).PME/Pi与PI正相关,与微血管异型指数负相关(P＜0.05).成熟血管数目、周长、直径及动脉数目与PME/ATP均相关(P＜0.05).PDE/Pi与成熟血管间距也为正相关(P=0.041,r=0.533),与LEP有关的因素包括平均灌注分数、EES和微血管总面积(P＜0.05).结论 HCC的pHi、Pi、β-ATP、PME/PDE都高于肝脏,PDE/ATP、PDE/Pi则相反;HCC血管生成的异质性影响~(31)P-MRS检测的各个代谢物的水平.     

Abil在肝细胞癌中的表达及临床意义

目的 研究Abil在肝细胞癌(HCC)组织中的表达情况及其临床意义.方法 采用RT-PCR法检测40例HCC组织及相应癌旁肝组织标本中Abil mRNA的表达情况;免疫组织化学法检测加例HCC组织及相应癌旁肝组织标本中Abil蛋白的表达情况;结合临床病理及随访资料分析Abil表达水平与HCC侵袭转移及预后的关系.结果 Abil mRNA在HCC组织中的表达水平高于相应的癌旁组织(1.32±0.75比0.74±0.52,P<0.05);Abil mRNA在结节性肝癌组织中的表达水平亦明显高于孤立性大肝癌组织(1.72±0.83比1.14±0.57,P<0.05).Abil蛋白主要表达于HCC细胞的胞质内,其表达水平与肿瘤结节数目、是否有包膜、静脉癌栓及Edmondson-Steiner分级密切相关(P<0.05),而与HCC患者的性别、有无肝硬化及肿瘤直径无明显相关性(P>0.05).Abil蛋白高表达组HCC患者的复发转移率明显高于低表达组患者(P<0.05);生存率则明显低于低表达组患者(P<0.02).结论 Abil在HCC组织中的表达水平较癌旁组织高,其表达水平与HCC的结节数目、是否有包膜、静脉癌栓、Edmondson-Steiner分级及临床预后密切相关.     

不同剂量纳洛酮后处理对大鼠局灶性脑缺血再灌注损伤的影响

目的 探讨不同剂量纳洛酮后处理对大鼠局灶性脑缺血再灌注损伤的影响.方法 成年sD大鼠88只,体重270～330 g,随机分为4组(n=22):假手术组(S组)、脑缺血再灌注组(IR组)和不同剂量纳洛酮后处理组(N_(1,2)组).除S组外,其它3组均采用阻断右侧大脑中动脉90 min、再灌注24 h的方法制备局灶性脑缺血再灌注损伤模型.N_(1,2)组于再灌注即刻分别腹腔注射纳洛酮1、10 mg/kg,S组和m组给予等容量生理盐水.分别于再灌注2、24 h时测定大鼠神经功能障碍评分(NDS);再灌注24 h时测定脑梗死面积和脑组织微管相关蛋白2(MAP2)的表达水平和脑组织血浆容量、徽血管直径和长度.结果 与S组相比,IR组、N_(1,2)组NDS评分均升高,脑梗死面积增大,脑组织MAP2表达水平下调,缺血侧脑组织血浆容量降低,微血管直径和长度减小(P<0.05);与IR组相比,N_2组NDS评分降低,脑梗死面积减小,脑组织MAP2表达水平上调,缺血侧脑组织血浆容量升高,微血管直径和长度增大(P<0.05),N_1组上述指标差异无统计学意义(P>0.05);与N_1组相比,N_2组NDS评分降低,脑梗死面积减小,脑组织MAP2表达水平上调,缺血侧脑组织血浆容量升高,微血管直径和长度增大(P<0.05).结论 纳洛酮后处理可减轻大鼠局灶性脑缺血再灌注损伤,且呈剂量依赖性.     

婴幼儿肺动脉闭锁合并室间隔缺损的肺组织形态学改变

目的观察婴幼儿肺动脉闭锁的肺组织形态学改变,了解体循环血流对肺组织发育的影响。方法2000年1月至2003年12月有肺组织病理切片资料的22例肺动脉闭锁合并室间隔缺损(PA-VSD)病儿作为病变组,4～36月龄。全部病例左、右肺动脉有融合,1例同时合并动脉导管未闭(PDA)和体-肺动脉侧支,3例合并体-肺动脉侧支,其余病例合并PDA。5例4～18月龄非心、肺源性疾病死亡的婴幼儿作为对照组。形态半定量测量肺细小动脉平均中膜厚度百分比(MT%)和中膜面积百分比(MS%),单位面积肺细小动脉数目(APSC),单位面积肺泡数(MAN),平均肺泡内衬间隔(MLI),肺实质占同切片肺总面积比例(PPA%)和单位面积肺泡数/肺细小动脉数比(AAR)。结果病变组肺泡的内径增大,单位面积肺泡数目减少,肺实质占同切片肺总面积比例减少,差异有统计学意义(P<0.05)。病变组肺细小动脉内、外弹力板间距以及MT%和MS%与对照组之间差异无统计学意义(P>0.05)。病变组血管MT%从6.43%～25.85%,MS%从15.45%～39.79%。2例有较大的体-肺动脉侧支供血的病婴由于局部肺血增多导致中膜增厚。病变组的APSC低于对照组,AAR高于对照组,P<0.05。结论肺循环血量明显影响肺细小动脉的增殖程度;动脉导管和(或)体-肺动脉侧支为肺循环提供的血流远不能满足外周肺血管的发育;体-肺动脉侧支不仅未能增加肺的血供,反而可能使外周肺血管出现萎缩。肺循环血流减少对肺细小动脉发育的影响大于对肺泡发育的影响。     

3TSR抑制裸鼠胰腺癌血管生成及其与VEGF表达的关系

目的 研究血管形成抑制荆3TSR对胰腺癌血管形成的影响,并探讨其与血管内皮生长因子(vasularendothelial growth factor,VEGF)表达的关系.方法 建立裸鼠原位胰腺癌模型,进行随机干预实验,实验分为对照组、3TSR1组(每天腹腔注射3TSR 1 mg/kg),3TSR2组(每天腹腔注射3TSR 2 mg/kg),3TSR3组(每天腹腔注射3TSR 3 mg/kg),每组7只.干预3周后,检测瘤体体积、肿瘤微血管指标,用ELISA法测定外周血VEGF含量,RT-PCR法测定肿瘤组织VEGF mRNA的表达.结果 治疗组平均肿瘤体积均低于对照组,差异有统计学意义(P<0.05),其中3TSR2组和3TSR3两组均低于3TSR1组,差异有统计学意义(P<0.05).治疗组平均微血管教、平均微血管面积及平均微血管密度均低于对照组,其中3TSR2和3TSR3两组其平均微血管面积和平均微血管密度低于3TSR1组,差异有统计学意义(P<0.05).VEGF外周血舍量对照组为(85±21)pg/ml,3TSR1组为(36±13)pg/ml,3TSR2组为(30±9)pg/ml,3TSR3组为(28±7)pg/ml.治疗组VEGF含量均低于对照组,差异有统计学意义(P<0.05).RT-PCR提示治疗组的VEGF mRNA含量低于对照组,差异有统计学意义(P<0.05),其中3TSR2和3TSR3两组均低于3TSR1组,差异有统计学意义(P<0.05).结论 3TSR能显著减小肿瘤体积,抑制微血管生长.其机制可能与抑制 VEGF表达有关.本研究为3TSR的临床前期应用提供了一定实验基础.     

基于肝细胞癌磁共振成像强化模式的术前微血管侵犯预测研究

目的探讨肝细胞癌(HCC)患者术前肿瘤MRI影像学特征与强化模式在预测微血管侵犯(MVI)中的价值。方法收集2017年1月至2019年6月在宁夏医科大学总医院行MRI检查并在肝胆外科行手术切除的孤立性HCC患者临床资料,按照术后病理诊断分为MVI(+)与MVI(-)两组,分析MVI与HCC的扩散加权成像(DWI)信号、强化模式、强化类型等影像学特征之间的关系。结果最终纳入HCC患者84例,其中男性65例,女性19例,年龄(54.94±11.51)岁。MVI(+)组46例,MVI(-)组38例,两组患者的肿瘤最大径分别为(7.08±3.45)cm和(4.28±2.47)cm,差异有统计学意义(P<0.01)。单因素分析表明,HCC MRI影像学特征指标DWI信号、包膜是否完整、强化模式、肿瘤边缘是否光整、是否存在瘤周异常强化和瘤内动脉,两组患者间差异均有统计学意义(均P<0.05);而T1加权成像信号、T2加权成像信号、病灶是否含脂,两组间差异无统计学意义(均P>0.05)。logistic回归分析表明肿瘤最大径>6.33 cm、3/4型强化模式、肿瘤边缘不光整为MVI(+)的独立危险因素(均P<0.05)。ROC曲线分析表明联合诊断的截断值为0.53、曲线下面积为0.881、敏感性0.870、特异性0.789、约登指数0.659。结论利用多因素logistic回归模型联合ROC曲线分析可以根据HCC MRI影像学特征进行术前HCC MVI预测。     

绿茶多酚改善环孢素A抑制血管舒张的作用

目的 观察绿茶多酚(GTP)对环孢素A(CsA)抑制血管舒张作用的改善,并探讨其机制.方法 将30只SD大鼠随机平均分为3组:CsA组、对照组和CsA+GTP组.建模5周后,检测体质量、肾功能:血尿素氮(BUN)、肌酐(Cre);并取胸主动脉环,观察乙酰胆碱(Ach)诱发的血管舒张反应、左旋硝基精氨酸甲酯(L-NAME)和吲哚美辛预处理对舒张反应的影响、去内皮细胞的血管舒张反应.并检测血管组织一氧化氮(NO)水平.结果 实验5周后,CsA组大鼠体质量(253.2±8.1)g低于对照组(292.1±9.5)g;CsA+GTP组体质量(287.9±9.7)g高于CsA组;CsA组BUN、Cre含量高于对照组;CsA+GTP组BUN、Cre低于CsA组;差异均有统计学意义(P<0.05).CsA组大鼠Ach引起的动脉环的最大舒张度为(42.5±4.3)%,低于对照组的(81.2±7.6)%和CsA+GTP组的(70.1±6.5)%,差异有统计学意义(P<0.05).用L-NAME预处理后,CsA组和CsA+GTP组动脉环的舒张幅度分别为(40.3±3.7)%和(45.8±4.2)%,均低于对照组的(79.4±6.8)%;用吲哚美辛预处理后对照组和CsA+GTP组的舒张反应高于CsA组;差异均有统计学意义(P<0.05).去内皮细胞的各组血管中,血管舒张反应被明显抑制,各组血管的舒张百分比差异无统计学意义(P>0.05).CsA组大鼠血管组织中NO含量显著低于对照组和CsA+GTP组,差异有统计学意义(P<0.05).结论 CsA可导致血管组织NO水平下降,引起NO介导的内皮依赖性血管舒张功能异常.应用绿茶多酚后,则升高其血管组织中NO水平,改善内皮依赖性的血管舒张功能.     

胰腺癌扩大根治术中的血管处理

目的 探讨联合门静脉-肠系膜上静脉切除的胰腺癌扩大根治术的临床意义和手术方法 ,以及术中医源性血管损伤的处理方法 .方法 回顾性分析242例胰腺癌扩大根治术患者临床资料,所有患者分为三组,A组为门静脉/肠系膜上静脉切除组(n=51),B组为术中发生医源性血管损伤组(n=5),C组为未行血管处理组(n=186),比较三个组的手术时间、术中输血量、血管阻断时间、平均住院天数、术后并发症及术后生存分析.结果 三个组手术时间分别为(442.85±102.32)min、(348.62±92.31)min和(315.00±83.43)min,术中平均输血量为(1430.83±1092.43)ml、(1420.22±794.41 ml)和(928.19±571.57)ml,手术时间和术中输血量相比差异有统计学意义(P<0.05),平均住院天数、术后并发症发生率差异无统计学意义(P 0.05).合并门静脉/肠系膜上静脉切除的胰腺腺癌患者术后中位生存期18.4个月,不合并门静脉/肠系膜上静脉切除组的胰腺腺癌患者术后中位生存期16.1个月,生存分析两者无明显差异(P 0.05).51例联合血管切除的患者中,行血管壁部分切除7例,行血管节段切除44例,44例血管节段切除患者中38例行端端吻合,6例行间置移植物,血管切除长度平均(2.92±1.35)cm;5例术中医源性动脉损伤的血管分别为肝动脉1例,肠系膜上动脉1例,腹腔干3例,处理方式为4例行端端吻合,1例行局部修补.结论 积极合理的开展联合门静脉/肠系膜上静脉切除的胰腺癌扩大根治术可以提高手术切除率,改善患者生活质量.由于局部的解剖关系复杂,术中较易发生医源性血管损伤,应引起术者重视并加以正确处理.     

经皮椎体成形术治疗骨质疏松性椎体压缩性骨折术中采用椎旁神经阻滞的镇痛效果

目的 探讨经皮椎体成形术(PVP)治疗骨质疏松性椎体压缩性骨折(OVCF)术中采用椎旁神经阻滞的镇痛效果.方法 2020年1月—2020年8月,华侨大学附属德化医院采用PVP治疗OVCF患者60例,其中30例采用椎旁神经阻滞麻醉(神经阻滞组),30例采用传统局部麻醉(局部麻醉组).比较2组手术时间、住院时间、住院总费用、术中平均动脉压和心率变化,及手术前后疼痛视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI).结果 2组手术时间、住院时间、住院总费用差异均无统计学意义(P>0.05).神经阻滞组患者术中各时间点的平均动脉压、心率与术前比较,差异无统计学意义(P>0.05);局部麻醉组患者术中各时间点的平均动脉压、心率均较术前升高,差异有统计学意义(P<0.05).2组术后VAS评分、ODI均较术前明显降低,差异有统计学意义(P<0.05);神经阻滞组术中、术后1 d、术后1个月VAS评分低于局部麻醉组,差异有统计学意义(P<0.05);神经阻滞组术后1 d、术后1个月ODI低于局部麻醉组,差异有统计学意义(P<0.05);2组术后3个月VAS评分、ODI差异无统计学意义(P>0.05).结论 PVP治疗OVCF术中采用椎旁神经阻滞麻醉并未增加风险、手术时间及住院费用,术中血流动力学相对稳定,且可有效缓解患者术中、术后早期疼痛,值得临床推广应用.     

肝脏神经内分泌肿瘤与肝细胞癌的CT影像学特征分析

目的探讨肝脏神经内分泌肿瘤(NENs)与肝细胞癌(HCC)的CT表现特征的差异。方法回顾性分析笔者所在医院于2011年6月至2016年6月期间收治的、经病理学检查证实的42例肝脏NENs患者和49例HCC患者的临床资料和CT影像学资料,按病灶直径是否≥3 cm进行分层,比较不同分层内的肝脏NENs患者和HCC患者的CT征象。结果在肿瘤直径3 cm的患者中,肝脏NENs组和HCC组患者的病灶直径、病灶边界、假包膜情况、平扫密度、富血供情况、动脉期强化程度、动脉期强化方式、肝内子灶、肝包膜凹陷、肿瘤新生动脉、动静脉受侵、门静脉癌栓、淋巴结直径及淋巴结强化程度比较差异均无统计学意义(P0.05),但2组患者的病灶位置、病灶形状及门静脉期强化方式比较差异均有统计学意义(P0.05),与HCC组比较,肝脏NENs组患者的病灶多位于全肝,病灶形状多呈类圆形,门静脉期强化方式多为持续强化。在肿瘤直径≥3 cm的患者中,肝脏NENs组和HCC组患者的病灶直径、病灶边界、平扫密度、富血供情况、动脉期强化程度、动脉期强化方式、肝内子灶、肝包膜凹陷、门静脉癌栓、淋巴结直径及淋巴结强化程度比较差异均无统计学意义(P0.05),但2组患者的病灶位置、假包膜情况、病灶形状、门静脉期强化方式、肿瘤新生动脉及动静脉受侵情况比较差异均有统计学意义(P0.05),与HCC组比较,肝脏NENs组患者的病灶多位于全肝,多无假包膜形成,多呈分叶状,门静脉期强化多呈持续强化,肿瘤多无新生动脉形成,且动静脉多未受侵。结论无论病灶直径是否≥3 cm,肿瘤位置、病灶形状及门静脉期强化方式均有助于鉴别肝脏NENs与HCC。当病灶直径≥3 cm时,肿瘤假包膜、肿瘤内新生动脉、动静脉受侵犯等有助于鉴别肝脏NENs与HCC。     

Immunohistochemical Analysis of Vascular Endothelial Growth Factor and Hepatocyte Growth Factor,and Their Receptors,in Transplanted Islets in Rats

Purpose. Our previous studies showed that transplanted islets increasingly express a marker of neovascularization, platelet endothelial cell adhesion molecule-1 (PECAM-1), as well as vascular endothelial growth factor (VEGF). Hepatocyte growth factor (HGF) is another stimulator of neovascularization. In this study, we examined the expression of these growth factors and their receptors; fetal liver kinase-1 (Flk-1) for VEGF and c-Met for HGF, to acertain whether VEGF and HGF play a role in the neovascularization of transplanted islets. Methods. Islets were isolated from male Lewis rats by collagenase digestion and the discontinuous dextran gradient method, then transplanted into the bilateral subnephrocapsular space. The kidneys were excised 1–28 days after transplantation, then fixed in formaldehyde and embedded in paraffin. Serial slices were immunostained for VEGF, HGF, Flk-1, or c-Met, respectively. Results. Islets in the normal pancreas were positively stained for VEGF, HGF, and c-Met; however, Flk-1 was only stained at the periphery of the islets. In the transplanted islets, staining for VEGF, HGF, and c-Met was positive, but Flk-1 was not stained. Moreover, staining for HGF and c-Met became stronger in the transplanted islets with time. Conclusion. These results suggest that HGF, rather than VEGF, may play a role in the neovascularization of transplanted islets.     

Biological activity of adult cavernous malformations: a study of 56 patients

OBJECT: Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions. METHODS: The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1alpha, and endoglin antibodies. Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB 1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1 alpha in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients. CONCLUSIONS: The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.     

Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations.

OBJECT: To date, both arteriovenous malformations (AVMs) and cavernomas have been considered to be congenital malformations. A recent survey of the literature has shown the potential for de novo generation of both familial and sporadic cavernomas as well as AVMs. Therefore, it was of interest to determine the biological behavior of these lesions in detail. METHODS: The proliferative and angiogenic capacities of the endothelium of 13 cavernomas and 25 AVMs obtained in patients recently treated (1997-1998) at one institution were studied. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth factor (VEGF) and its receptor Flk-1 was performed using standard staining procedures. Positive immunostaining of the nuclei of endothelial cells was observed in specimens of both AVMs and cavernomas for PCNA (80% of AVMs and 85% of cavernomas), and Flk-1 (80% of AVMs and 31% of cavernomas). Endothelial expression of VEGF in the 18 incompletely embolized AVMs was found in 72% of cases but only in 28% of the seven cases in which patients did not undergo endovascular treatment: it was found in 38% of cavernomas. Endothelial expression of MIB-1 was found in 12% of AVMs but in no cavernomas. CONCLUSIONS: These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.     

Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen involved in angiogenesis, wound healing, and inflammation. METHODS: Rats placed on low salt diet (LSD) or normal salt diet (NSD) were treated with cyclosporine (CsA) or vehicle (VH) and killed at 7 or 28 days. We studied the expression of VEGF and its receptors Flt-1 and KDR/Flk-1 mRNA by Northern and that of VEGF protein by Western blot. RESULTS: CsA induced VEGF mRNA and protein expressions at 7 and 28 days in LSD rats. At 7 days, CsA up-regulated the expression of Flt-1 and KDR/Flk-1 receptors; however, at 28 days, Flt-1 remained unchanged whereas KDR/Flk-1 expression declined. In NSD rats, in which the lesion did not develop, the expression of VEGF and its receptors remained similar to control. CONCLUSIONS: What causes VEGF to be up-regulated remains unclear. Further studies are needed to study the role of hypoxia and other cytokines in relation to VEGF in this model.     

Nitric oxide modulates vascular endothelial growth factor and receptors in chronic cyclosporine nephrotoxicity

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in angiogenesis, wound healing, and inflammation and exerts its effect via tyrosine kinase receptors, fms-like tyrosine kinase (Flt-1) and fetal liver kinase (Flk-1 or KDR). We have previously shown that VEGF is up-regulated in a model of chronic cyclosporine (CsA) nephrotoxicity and that l-arginine (l-Arg) improved while N-nitro-l-arginine-methyl ester (L-NAME) worsened fibrosis. We examined the role of nitric oxide modulation on VEGF in this model. METHODS: Pair-fed salt-depleted rats were administered CsA, CsA + L-NAME, CsA +l-Arg, vehicle (VH), VH + L-NAME or VH +l-Arg and were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to the mRNA expression of VEGF and its receptors Flt-1 and KDR/Flk-1 by Northern blot and the protein expression of VEGF by Western blot and immunohistochemical staining. RESULTS: While L-NAME worsened renal function and histology, l-Arg had the opposite beneficial effect in CsA-treated rats. VEGF mRNA and protein expressions increased with CsA, further increased with L-NAME and became significantly reduced with L-Arg. Flt-1 expression was similar in all groups. On the other hand, KDR/Flk-1 mRNA expression was modulated in a fashion similar to VEGF. Also, nitric oxide modulation did not have an effect on VH-treated rats. CONCLUSIONS: VEGF expression in chronic CsA nephrotoxicity is increased by nitric oxide blockade and decreased by nitric oxide enhancement. Moreover, VEGF probably exerted its effect via the KDR/Flk-1 receptor. The actions of VEGF in this model remain speculative, but it is probable that VEGF plays a role, either independently or through nitric oxide, in CsA-induced fibrosis.     

Angiotensin II regulation of vascular endothelial growth factor and receptors Flt-1 and KDR/Flk-1 in cyclosporine nephrotoxicity

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in angiogenesis, wound healing and inflammation. VEGF exerts its effect via the tyrosine kinase receptors Flt-1 and KDR/Flk-1. We have previously shown that VEGF is up-regulated in a chronic cyclosporine (CsA) nephrotoxicity model. Our current study examined the role of angiotensin II (Ang II) blockade with enalapril (E) or losartan (L) on VEGF in this model. METHODS: Pair-fed salt-depleted rats were administered vehicle, CsA, CsA + nilvadipine, CsA + hydralazine/hydrochlorthiazide (HCTZ), CsA + E or CsA + L, and were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to the mRNA expression of VEGF and its receptors Flt-1 and KDR/Flk-1 by Northern blot, and the protein expression of VEGF by Western blot. RESULTS: While all groups achieved similar blood pressures and creatinine clearances, the amelioration in nephrotoxicity was observed only with Ang II blockade. VEGF mRNA and protein expressions increased with CsA and became significantly reduced with Ang II blockade. Flt-1 expression was similar in all groups; it decreased early and remained low. On the other hand, KDR/Flk-1 mRNA expression was higher at seven days in all groups, except in the +E and +L groups where it was significantly lower, and then became further down-regulated at 28 days. CONCLUSIONS: The increased VEGF expression in chronic CsA nephrotoxicity seems to be related to up-regulation of Ang II. In addition, VEGF probably exerted its effect via the KDR/Flk-1 receptor. The actions of VEGF in this model remain speculative, but may be related to its effect on macrophage infiltration or matrix deposition.     

Expression of vascular endothelial growth factor and its fetal liver kinase-1 receptor in spinal cord and dorsal root ganglia after neurotomy of sciatic nerve in rats

egenerationofinjured peripheralnervesiscloselyrelatedtosomegrowthfactorssecretedbycentralneurons .Vascularendothelialgrowthfactor (VEGF)isapotentangiogenicfactor ,which possessesspecificmitogenicactivityforvascularendothelialcells ,stimulatestheformationofnascentbloodvesselsandenhancesvascularpermeability .1RecentevidencesindicatethatVEGFcanalsoactdirectlyonneuronstoinduceneurotrophiceffects.Forexample ,VEGF promotestheproliferationofculturedcerebralcorticalneurons ,stimulatestheaxonaloutg…     

铜宫内节育器和含吲哚美辛铜宫内节育器对大鼠子宫内膜血管内皮生长因子表达的影响

目的　研究置固定式铜宫内节育器 ( FCu-IUD)和固定式吲哚美辛铜宫内节育器 ( FICu-IUD)的大鼠子宫内膜组织中血管内皮生长因子 ( VEGF)及其受体 Flk-1的表达对子宫异常出血的影响。　方法　采用免疫组化 SP法检测 FCu-IUD组、FICu-IUD组大鼠子宫内膜组织 VEGF的表达及 Flk-1的定位 ,逆转录聚合酶链反应 ( RT-PCR)检测各组 VEGF m RNA的表达。以未置器一侧作为对照。　结果　 VEGF在子宫内膜腺上皮细胞、基质细胞及血管内皮细胞均有表达 ,Flk-1定位于血管内皮细胞及子宫内膜基质细胞的胞膜与胞浆。 FCu-IUD组、FICu-IUD组均有 VEGF m RNA扩增。 FCu-IUD组置器侧较对照侧 VEGF蛋白及 m RNA表达明显增加 ,FICu-IUD组置器侧与对照侧比较 ,VEGF表达无明显差异。而 FCu-IUD组与 FICu-IUD组比较 ,VEGF表达有显著差异。　结论　 Cu-IUD引起的子宫异常出血与 VEGF的增加有关 ,吲哚美辛减少 Cu-IUD引起的子宫异常出血的作用可能与通过抑制前列腺素合成从而 VEGF生成减少有关     

乳腺癌发生与演进过程中血管生成作用的评价

目的 探讨人乳腺癌前病变、原位癌及浸润性癌中CD34、血管内皮生长因子(VEGF)及其受体Flk-1/KDR的表达变化及血管生成异常与乳腺癌发生发展的关系.方法 应用免疫组织化学技术检测30例正常乳腺、30例普通性增生、30例非典型增生(AH)、20例导管内癌、50例浸润性导管癌组织中微血管密度(MVD)、VEGF及Flk-1/KDR的表达.结果 各组CD34、VEGF及Flk-1/KDR的表达程度不同,浸润性导管癌组最高.随病程演进MVD逐渐增加(P<0.05),VEGF及其受体Flk.1/KDR在血管内皮细胞表达渐进性增高(P<0.05),但在病程初期各主要指标改变不明显,显著变化始于AH阶段.MVD在AH与导管内癌组间差异无统计学意义(P>0.05),VEGF及Flk-1/KDR的表达在AH与导管内癌组间差异有统计学意义(P<0.05).结论 血管生成异常可能是乳腺癌发生过程中的早期事件.VEGF及Flk-1/KDR的表达异常可能是乳腺普通性增生-AH-乳腺癌这一癌性转化过程中血管生成异常的主要始动因素,其可能成为乳腺癌早期诊治的靶标.     

Gene expression of VEGF and its receptors Flk-1/KDR and Flt-1 in cultured and transplanted rat islets

BACKGROUND: Vascular endothelial growth factor (VEGF) and its two receptor tyrosine kinases, Flk-1/KDR and Flt-1, may play an important role in mediating the revascularization of transplanted pancreatic islets. METHODS: Using semiquantitative multiplex reverse-transcribed polymerase chain reaction we determined the gene expression of VEGF and its receptors in cultured and transplanted rat islets. RESULTS: After exposure of islet cells to hypoxia in vitro, increases were found in the gene expression of the VEGF120 and VEGF164 isoforms, with simultaneous increases in VE-cadherin, Flk-1/KDR, and Flt-1. In vivo studies consisted of analysis of islet grafts transplanted into both normal and diabetic recipients. Expression of both VEGF120 and VEGF164 in grafts was up-regulated for the first 2-3 days after transplantation, with the response being more prolonged in the diabetic rats. These increases were followed by reduced expression of VEGF on days 5, 7, and 9. Increases in the expression of VE-cadherin in islet grafts in normal and diabetic recipients tended to parallel VEGF expression, with the increases in both probably being caused by hypoxia. The early increases of VEGF expression were followed by a rise in the expression of VEGF receptors, which probably represents the early stages of angiogenesis. Graft expression of Flk-1/KDR and Flt-1 was enhanced at 3 and 5 days in the normoglycemic recipients, while in the diabetic recipients increases were found later on days 5, 7, and 14. CONCLUSIONS: The delayed expression of VEGF receptors in the diabetic recipients could reflect impaired angiogenesis caused by the diabetic milieu; this delay could contribute to the less outcomes of grafts transplanted into a hyperglycemic environment.