大肠癌患者血清MMP-9与VEGF水平的变化及意义

目的本文检测血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP-9)在大肠癌患者血清中的水平,探讨其与大肠癌恶性程度、浸润、转移的关系。方法用ELISA法对48例大肠癌患者及40例正常对照者血清VEGF和MMP-9进行检测。结果大肠癌患者血清VEGF、MMP-9的水平分别为(665.8±232.8)ng/L;(532.7±208.9)ug/L。显著高于对照组(391.6±135.2)ng/L;(317.8±132.2)ug/L(P<0.01)。并与组织分化程度、Duke’s分期有关。低分化者及C、D期患者较中、高度分化及A、B期高(P<0.01)。结论大肠癌患者血清VEGF和MMP-9水平增高,与肿瘤的组织分化程度、转移、分期有关,提示VEGF、MMP-9对大肠癌恶性程度的判断有一定的价值。     

Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease

OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD.     

TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo

Lymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well-known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 ± 5.0% vs. 40.6 ± 11.0%, T lymphocytes 84.6 ± 6.3% vs. 56.5 ± 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 ± 0.9% vs. 8.9 ± 3.6%), whereas that in HEV of axLN (19.0 ± 6.4% vs. 16.6 ± 6.0%) and PP (30.6 ± 6.1% vs. 33.9 ± 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo.     

血管夹对大鼠股动静脉损伤的实验研究

用１００、４５、１５ｇ力的血管夹，夹闭大白鼠股动静脉２０、６０和１２０ｍｉｎ，２４ｈ后观察其通畅情况，并经扫描电镜和光学显微镜观察股动静脉内皮细胞的损伤程度和血管内血栓形成。结果显示：前两种压力的血管夹在对股动脉只产生轻微损伤的情况下，对伴行股静脉可造成内皮细胞脱落，微小血栓形成等病理损伤。随夹闭血管时间的延长，内皮细胞损伤加重，血小板沉积和微血栓增多。血管夹对静脉的损伤和对其通畅率的影响尤应引起注意。     

子宫肌瘤患者外周静脉与子宫静脉血管内皮细胞生长因子水平测定及临床意义

目的:探讨血管内皮细胞生长因子(VEGF)在子宫肌瘤发生和肌瘤生长中的作用。方法:手术中暴露子宫静脉后,抽取子宫静脉血3ml,同时抽取非输液肢体外周静脉血3ml。抽取配对正常妇女外周静脉血3ml。ELISA法测定VEGF水平。测量子宫重量、肌瘤总重量、肌瘤数目和最大肌瘤最大径线值。结果:子宫肌瘤患者子宫静脉血和外周静脉血VEGF水平分别为159.38±25.63pg/ml和76.35±26.61pg/ml,对照人群外周静脉血VEGF水平为42.53±29.47pg/ml。子宫静脉血中的VEGF水平明显高于外周静脉血(P=0.019),子宫肌瘤患者外周静脉血中的VEGF水平明显高于对照人群外周静脉血的VEGF水平(P=0.013)。子宫重量、肌瘤总重量、肌瘤数目、最大肌瘤最大径线都与子宫肌瘤患者子宫静脉和外周静脉VEGF呈显著正相关。结论:VEGF可能参与了子宫肌瘤的生长和病情发展。     

低密度及氧化低密度脂蛋白对内皮细胞分泌肾上腺髓质素的影响

目的探讨低密度及氧化低密度脂蛋白对内皮细胞分泌肾上腺髓质素(ADM)的影响.方法利用培养的内皮细胞株ECV-304细胞,分别与不同浓度的低密度(50 100mg/L)、氧化低密度脂蛋白(50 100mg/L)及低密度脂蛋白(50 mg/L) 氧化低密度脂蛋白(50 mg/L)进行孵育,24 h后分别收集培养上清及细胞,用放免分析检测上清及细胞内肾上腺髓质素的含量.结果低密度脂蛋白对肾上腺髓质素的分泌无影响,而氧化型低密度脂蛋白能明显刺激ADM的分泌,二者合用的作用接近于100mg/L的OX-LDL.结论OX-LDL可能具有氧化LDL使其成为OX-LDL的作用,ADM的分泌可能是对细胞损伤的一种反应.