转染人VEGF165基因对大鼠胰岛移植物再血管化及生物学功能的影响

目的探讨转染人血管内皮生长因子（VEGF）基因对大鼠胰岛移植物再血管化和生物学功能的影响。方法实验分二步进行，首先构建携带人血管内皮生长因子165（hVEGF165）基因的重组腺病毒载体AdhVEGF165，用其按病毒／细胞的感染倍数（MOI）分别为10、100、500的比例在体外转染新鲜分离、纯化的近交系Lewis大鼠胰岛，检测体外培养的胰岛表达hVEGF165基因的情况；然后按MOI为10的比例在体外用AdhVEGF165转染Lweis大鼠胰岛，再经门静脉注射至近交系Lewis大鼠的肝脏内（VEGF组），并设不含hVEGF165基因的空载体转染对照组（GFP组）和磷酸盐缓冲液处理对照组（PBS液组），术后测定受鼠的血糖变化，进行静脉糖耐量试验（IVGTT），并观察受鼠肝脏中移植胰岛的组织学变化。结果体外转染hVEGF165基因的大鼠胰岛分泌至细胞外的hVEGF165的浓度显著高于未转染者（P〈0．01）。糖尿病大鼠移植转染hVEGF165基因的胰岛后，静脉注射葡萄糖后40、60、120min时的血糖水平显著低于GFP组和PBS液组（P〈0．05）；40min时体循环中胰岛素的浓度，VEGF组显著高于GFP组和PBS液组（P〈0．05）；VEGF组移植胰岛内CD34和胰岛素免疫组化染色的强度均高于GFP组和PBS液组。结论转染hVEGF165基因对胰岛移植物的再血管化和生物学功能有促进作用。     

IL-10在过敏性紫癜血管内皮损伤中的作用机制研究

目的　探讨白细胞介素 10 (IL 10 )在过敏性紫癜血管内皮损伤中的作用及机制。方法　建立人脐静脉内皮细胞 (HUVEC)培养模型 ,ELISA法检测过敏性紫癜患儿外周血单个核细胞 (PB MC)活化后培养上清IL 6、IL 1β、TNF α、IL 10等细胞因子的含量 ;AnnexinV/PI双染色法 ,流式细胞仪检测过敏性紫癜患儿PBMC培养上清所诱导的内皮细胞凋亡率。结果　①过敏性紫癜组PBMC体外刺激活化后IL 6、IL 1β、TNF α、IL 10等细胞因子的分泌量均明显高于对照组 (P <0 0 1) ,其培养上清诱导的内皮细胞凋亡率 (34 7± 10 3) %明显高于对照组 (3 6± 0 9) %。②抗IL 6、IL 1β、TNF α单克隆抗体联合阻断可明显降低过敏性紫癜患儿PBMC培养上清诱导的内皮细胞凋亡率 (2 2 6±5 9) % ,而抗IL 10单克隆抗体阻断则明显增加过敏性紫癜患儿PBMC培养上清诱导的内皮细胞凋亡率 (5 6 9± 16 5 ) %。③于过敏性紫癜患儿PBMC培养上清加入外源性IL 10 ,可明显降低IL 6、IL 1β、INF α等炎性细胞因子的表达 ,并明显降低内皮细胞凋亡率 (11 8± 3 1) %。结论　IL 10作为机体炎症反应负反馈调节过程中的一个重要枢纽 ,在过敏性紫癜炎症因子所介导的血管内皮损伤中起重要的保护作用。     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

bevacizumab治疗乳腺癌的基础和临床研究

分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。     

豚鼠耳蜗微血管内皮细胞体外通透性的研究

目的　研究豚鼠耳蜗微血管内皮细胞的体外通透性特征。方法　在成功建立豚鼠耳蜗微血管内皮细胞体外通透性模型的基础上 ,研究该体外模型跨细胞电阻及对12 5I 牛血清白蛋白的通透性。结果　①耳蜗微血管内皮细胞在培养增殖过程中其跨细胞电阻呈动态变化过程 ,以 5× 10 4/cm2 的细胞密度接种时 ,7d左右电阻到达峰值 ,其跨细胞电阻峰值大小为 (118 9± 18 5 )Ω/cm2 ;②体外模型中加入12 5I 牛血清白蛋白后 ,其通透性呈上升期抛物线型曲线 ,90min内几乎呈直线。结论　跨细胞电阻及对12 5I 牛血清白蛋白变化曲线能反映体外耳蜗微血管内皮细胞的通透性特征     

糖尿病大鼠视网膜血管内皮生长因子与一氧化氮的变化

目的：探讨糖尿病大鼠视网膜血管内皮生长因子（VEGF）与一氧化氮（NO）的变化及其在糖尿病视网膜病变（DR）发生发展过程中的作用。方法：选择健康成年SD大鼠，随机分成正常对照组，糖尿病1月（DM1），糖尿病3月（DM3）和糖尿病5月（DM5）组，一次性腹腔注射链佐菌素（STZ）诱发糖尿病模型，应用免疫组织化学方法观察各组视网膜组织VEGF的表达情况，并检测各组视网膜组织中一氧化氮合酶（NOS）活性和NO含量变化。结果：3个月时，糖尿病大鼠视网膜VEGF表达增强，NOS活性增强，NO含量增高，5个月时，糖尿病大鼠视网膜表达进一步增强，而NOS活性开始减弱，NO含量减少，结论：糖尿病大鼠视网膜VEGF的过度表达和NOS活性，NO含量的变化在DR的发生发展过程中起重要作用。     

血管内皮生长因子与乳腺癌临床病理因素及预后的关系

目的：探讨血管内皮生长因子在乳腺癌中的表达情况及其与预后的关系。方法：采用免疫组化法对1985年至1986年手术治疗的109例乳腺癌的原发灶进行血管内皮生长因子（VEGF）和微血管密度（MVD）检测，并与临床病理资料进行比较分析。结果：VEGF强表达组淋巴结转移率（52．2％）和病理分级明显高于弱表达且（23．5％，P＜0．05）；随VEGF表达强度的增加，生存率（5年、10年、15年）呈下降趋势，但无明显差异；VEGF与肿瘤大小、绝经状况、雌孕激素受体之间未见相关性。结论：VEGF表达与乳腺癌淋巴结转移和病理分级呈正相关，与预后呈负相关趋势，是估计恶性程度的有用指标，对判断预后有参考价值。     

Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control

Background  Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and angiogenesis. It has been reported that vascular endothelial growth factor (VEGF) is overexpressed in lesional psoriatic skin and its serum levels are significantly elevated in patients with moderate to severe disease.
Objective  This study aims to evaluate the possible role of VEGF in the pathogenesis of psoriasis, and its significance as an indicator of disease severity and control.
Methods  Thirty patients with moderate to severe psoriasis and 10 healthy controls were subjected to baseline evaluation of VEGF. Patients were divided into three groups according to the received treatment: psoralen plus ultraviolet A (PUVA) thrice weekly (group 1), acitretin 50 mg daily (group 2), and combined PUVA twice weekly and acitretin 25 mg daily (group 3).Treatment continued for 16 weeks or up to clinical cure. Every patient was subjected to severity evaluation by Psoriasis Area and Severity Index (PASI) and measurement of serum VEGF before and after treatment.
Results  Mean serum levels of VEGF were significantly elevated in patients (327 ± 66.2 pg/mL) than control subjects (178 ± 83.4 pg/mL). A highly significant correlation was found between VEGF and PASI score, but not with other variables. The best clinical response, the least side-effects and the highest reduction of VEGF serum levels were achieved by the combined therapy.
Conclusion  The present study supported the proposed role of VEGF in the pathogenesis of psoriasis, and suggested that it could serve as a good indicator of disease severity and control.