降糖起萎合剂对糖尿病微血管病变大鼠阴茎海绵体糖基化终产物含量的影响

目的探讨降糖起萎合剂对糖尿病微血管并发症大鼠阴茎海绵体沉积的糖基化终产物(AGEs)的抑制作用.方法根据AGEs具有产生荧光的特点,通过测定其荧光强度,间接表示阴茎海绵体内AGEs的含量.结果及结论降糖起萎合剂对糖尿病微血管并发症大鼠阴茎海绵体沉积的荧光AGEs有较强的抑制作用.     

血脑屏障上γ-氨基丁酸转运体及其相关基因的分布

目的　明确γ 氨基丁酸 (GABA)转运体 (GAT)超家族成员基因在血脑屏障上的分布及寻找相关的新成员。方法　在体灌注磁珠标记脑微血管 ,体外磁选获得不含完整神经细胞的微血管片段 ;设计GAT超家族成员基因的同源引物 ,以脑微血管tRNA为模板 ,采用RT PCR扩增目的片段 ,测序聚丙稀酰胺凝胶电泳分离特异扩增产物 ,对特异条带分别克隆、测序。应用Blast软件将测得序列与Genebank中的所有已知序列比对分析。结果　对纯化血管的tRNA进行RT PCR ,产物经PAGE电泳分离 ,分别克隆、测序 ,获得B1～B7共 7个不同的核苷酸序列。B3、B5的全序列与大鼠GAT 2、BGT 1的部分序列高度同源 ,B7的全序列与牛磺酸转运体TAUT的部分序列高度同源 ,其它 4个表达序列标签 (EST)B1、B2、B4、B6已提交Genbank的dbEST ,B1(Genebank接受号 :CF35 896 5 )、B2 (CD5 6 8346 )、B4 (CF35 896 6 )和B6(CD5 6 8347)的部分序列与Genbank中的一些序列有一定的同源性 ,但与GAT成员的同源性低。结论　血脑屏障上存在GAT 2、BGT 1两个GAT亚型和TAUT基因 ,可能负责跨血脑屏障的GABA转运。与GAT有关的 4个EST序列的基因及功能有待进一步阐明。     

Enhancement of Transport of D-Melphalan Analogue by Conjugation with L-Glutamate across Bovine Brain Microvessel Endothelial Cell Monolayers

Abstract

In this paper, the L-glutamate (L-Glu) transport system was targeted to improve the delivery of a model compound, p-di(hydroxyethyl)-amino-D-phenylalanine (D-MOD), through the blood-brain barrier (BBB) in vitro cell culture model. D-MOD is an analogue of an antitumor agent D-melphalan. To target the L-Glu transport system, D-MOD was conjugated to L-Glu to give D-MOD-L-Glu conjugate. D-MOD and D-MOD-L-Glu transport properties were evaluated using the bovine brain microvessel endothelial cell (BBMEC) monolayers. The results suggest that D-MOD-L-Glu conjugate permeates through the BBMEC monolayers more readily than the parent D-MOD. The improvement of transport may be due to the recognition of D-MOD-L-Glu by the L-Glu transport system. The transport mechanism was evaluated using several different experiments including: (a) concentration-dependent studies; (b) temperature-dependent studies; (c) substrate inhibition studies; and (d) metabolic inhibitor studies. The D-MOD-L-Glu transport was inhibited by the change of temperature from 37°C to 4°C. At higher concentrations, the transport of D-MOD-L-Glu reached plateau due to saturation. Furthermore, some amino acids (i.e., L-Glu, L-Asp, D-Asp, and L-Gln) inhibited the transport of D-MOD-L-Glu; presumably the conjugate was competing with these amino acids for the same transport system. Metabolic inhibitors (i.e., 2,4-dinitrophenol and sodium azide) suppressed the transport of the conjugate. However, the conjugate was not transported by monocarboxylic acid, dipeptide and neutral amino acid transporters. In conclusion, the L-Glu transport system can be utilized to facilitate a non-permeable drug across the BBB by conjugating the drug with L-Glu amino acid.     

Angiogenesis in salivary gland tumors: from clinical significance to treatment

Introduction: Salivary gland tumors (SGTs) represent a rare cancer entity, consisting of various morphological features that complicate diagnosis. Their diversity in terms of morphology and clinical course makes defining risk factors difficult, while the molecular steps responsible for SGT development remain unclear. Angiogenesis, a hallmark of cancer development, is considered as an attractive target.

Areas covered: This review aims to summarize the available research regarding angiogenesis in SGTs from clinical significance to treatment options.

Expert opinion: The available data suggest that microvessel density (MVD) evaluation may be capable of discriminating between benign and malignant SGTs, while the use of CD105 antibody seems to be the most suitable. Substantial evidence also suggests that MVD and VEGF expression could be used as prognostic factors in malignant SGTs. Although several agents have shown antiangiogenic activities in adenoid cystic carcinoma cells and xenograft tumors, limited effectiveness in the existing clinical trials was noted. Further studies are strongly recommended for the validation of already well-known and the identification of novel prognostic and predictive angiogenic markers. There is also a strong demand for relatively larger cohorts, homogenous samples referring to same histological SGT subtypes and including an equivalent number of low- and high-grade SGTs.     

大鼠局灶性脑缺血再灌注后皮质神经元微血管构筑和血脑屏障的变化及丁苯酞的保护作用

目的:观察大鼠脑缺血再灌注损伤后皮质微血管的变化,探讨丁苯酞对其作用。方法:线栓法制备大鼠脑缺血再灌注模型;单宁酸-氯化铁媒染法显示大脑皮质微血管,Mivnt图像分析系统定量分析微血管密度(MVD)和微血管面积密度(MVA);十湿重法检测脑含水量,透射电镜观察血脑屏障超微结构。结果:与假手术组相比,缺血再灌注组大鼠皮质微血管绝大部分闭合或僵直,MVD和MVA显著下降,脑含水量明显升高,电镜观察微血管腔狭窄,内皮细胞核固缩。丁苯酞组微血管形态好转,MVD和MVA升高,脑水肿和血脑屏障损伤程度均减轻。结论:丁苯酞可改善大鼠脑皮质微血管形态,减轻脑水肿和血脑屏障损伤,对脑缺血再灌注损伤有一定的预防性保护作用。     

糖尿病微血管病变发生机制研究现状

糖尿病微血管病变是糖尿病慢性并发症的病理基础,病理机制涉及内皮受损及一氧化氮合成减少、多元醇代谢异常、糖化反应的亢进、氧化应激、蛋白激酶C激活等多个方面,现对糖尿病微血管病变的研究现状进行探讨,以提高对糖尿病微血管病变的认识水平。     

CD34和VEGF在肝癌组织中的表达及与肿瘤血管生成的相关性

目的探讨CD34和血管内皮生长因子（VEGF）在肝细胞肝癌（HCC）组织中的表达及微血管密度（MVD）的临床病理意义。方法应用链霉素扰生物素蛋白-过氧化物酶法（S—P法）对50例HCC患者进行肿瘤血管生成免疫组织化学检测。对CD34阳性血管进行MVD计数．对VEGF进行半定量计数，并分析与HCC的临床病理特征的关系及意义。结果CD34在HCC组织中呈广泛、窦隙状表达，MVD值在有汇管区癌栓和肝内转移者高于无汇管区癌栓和无肝内转移者（P〈0．05），VEGF表达的阳性率在有汇管区癌栓和肝内转移者明显高于元汇管区癌栓及无肝内转移者（P〈0．05）。MVD值在VEGF阳性组和阴性组之间差异有显著性（P〈0．05）。结论HCC中MVD值和VEGF阳性表达率明显增高，由自分泌和旁分泌产生的VEGF通过促进HCC肿瘤血管生成而促进HCC的生长和转移。     

探索学习环境对脑梗死大鼠学习记忆能力及缺血侧海马区微血管密度的影响

目的研究探索学习环境对局灶性脑梗死大鼠学习记忆能力及缺血侧海马区微血管密度的影响。方法 80只Sprague-Dawley大鼠开颅电凝右侧大脑中动脉,随机分为标准环境组(SE组,n=40)和探索学习环境组(LE组,n=40)。分别于术后7d、28 d进行Morris水迷宫测试;术后1 d、3 d、7 d、14 d、28 d,CD34免疫组织化学法测定海马区微血管密度。结果 LE组Morris水迷宫测试成绩显著优于SE组(P0.001)。术后7 d起,LE组缺血侧海马区微血管密度高于SE组(P0.05)。结论探索学习环境可促进脑梗死大鼠微血管新生,有利于学习记忆功能恢复。