骨软骨连接处血管生成与骨关节炎

健康成年人关节软骨内既不舍血管,也不含神经.近年研究证实骨关节炎患者软骨中可见骨软骨连接处血管向软骨内延伸,而骨关节炎软骨内血管生成的具体机制尚不清楚,所涉及的各种因素正成为目前研究的热点.该文基于有关文献,就软骨血管生成的结构、代谢改变机制,及其在骨关节炎发病过程中的作用和临床病理意义作一综述.     

巨噬细胞炎症蛋白-1α在大鼠主动脉斑块中的表达及其与血管生成的关系

目的探讨巨噬细胞炎症蛋白-1α（MIP-1α）在大鼠主动脉稳定斑块和不稳定斑块内的分布、与血管新生之间的关系及其在不稳定斑块形成过程中的可能作用。方法将24只Wistar大鼠随机分为正常对照组（8只，C组）和动脉粥样硬化模型组（16只，A组）。3个月后，免疫组织化学SABC法检测MIP-1α蛋白的表达情况，鼠单克隆抗体CD34计数微血管密度（MVD）。结果模型组中，MIP-1α阳性表达率85、71％，正常组MIP-1α无表达（0）（P〈0．01）；模型组中MVD（15．54±4．22）明显高于正常组（0）（P〈0．01）；不稳定斑块组MIP-1α（28．99±3．43）、MVD（24．12±4．34）均高于稳定斑块组（分别为19．76±5．02，17．45±3、71，P〈0．05），MIP-1α蛋白表达与CD34呈正相关（r=0．671，P〈0．05）。结论不稳定斑块组较稳定斑块组的MIP-1α仅含量高，提示斑块内MIP-1α仅含量是影响斑块稳定性的重要因素，MIP-1α仅可以通过促进动脉粥样硬化斑块内血管生成，从而增加斑块的不稳定性。     

骨关节炎的诊治与研究进展

骨关节炎(osteoarthritis,OA)是影响人类健康最常见的关节疾患之一,人群发病率约为2%～6%,是导致50岁以上人群功能残疾、造成经济损失和影响社会发展的主要疾病之一.骨关节炎具有临床、病理和影像学多重定义;在其疾病发生与发展过程中,在全身因素和局部因素综合作用下,关节软骨发生生化、结构和代谢改变,最终出现关节软骨软化、破溃和局部剥脱以及关节边缘骨与软骨赘生物形成等病理改变,并引起相应临床症状;骨关节炎相关的滑膜炎症是软骨基质降解产物引起的继发性改变,滑膜炎性病变在骨关节炎的发生中不是旁观者,而是关节结构破坏的参与者,促进了骨关节炎的病程进展.骨关节炎的治疗目标是控制疼痛、改善关节功能和生活质量,尽可能避免治疗的毒副作用.目前,骨关节炎缺乏治愈的手段.但是,针对患者设计的个体化治疗方案可以减轻疼痛、保持或改善关节活动度,减缓关节功能的受损.应重视对患者的教育和康复治疗,特异性COX-Ⅱ抑制剂减少了胃肠道副反应事件的发生.当内科保守治疗无效,而日常活动进行性受限时,应该考虑关节镜清理、截骨术和关节置换手术等外科治疗.软骨移植、氨基葡萄糖、针对炎性因子或细胞内与炎症相关的信号分子的生物治疗手段为骨关节炎的治疗开辟了新的研究方向.     

炎症与血管钙化关系的研究进展

血管钙化(VC)是动脉粥样硬化、高龄、糖尿病、慢性肾脏病(CKD)等共同的病理改变,与心血管疾病高发病率和高死亡率密切相关。目前认为血管钙化是一个多因素参与调节的复杂的生物学过程,炎症可能通过直接或间接的方式参与血管钙化的形成与进展。本文就炎症与血管钙化的关系作一综述。     

血管生成与动脉生成

出生后的血管再生方式主要包括血管生成和动脉生成。血管生成与动脉生成过程中可以发现两者在发生的部位、诱发和调节因素、结果方面有着一定的区别和联系。大部分的缺血性血管疾病需要同时促进血管生成和动脉生成。因此 ,联合应用生长因子、炎症因子和细胞来促进血管生成与动脉生成 ,恢复缺血区的血液供应、改善组织细胞的氧和营养物质供给 ,才能全面的治疗缺血性血管疾病 ,它将成为缺血性血管疾病治疗的发展方向     

促血管生成素与胃癌血管生成的关系

目的探讨促血管生成素与胃癌微血管生成的关系，以及与胃癌微循环中存在的各种血管生长因子问的相互调控作用。方法采用文献回顾的方法，对有关促血管生成素和胃癌血管生成的关系进行综述。结果促血管生成素在胃癌微循环中的表达与胃癌的血管生成有关系，但与各种血管生成因子之间的相互调控作用仍存在争议。结论促血管生成素在胃癌微小血管的萌芽、发展、凋亡等一系列过程中扮演着重要的角色。     

血管生成与动脉生成

出生后的血管再生方式主要包括血管生成和动脉生成。血管生成与动脉生成过程中可以发现两者在发生的部位、诱发和调节因素、结果方面有着一定的区别和联系。大部分的缺血性血管疾病需要同时促进血管生成和动脉生成。因此，联合应用生长因子、炎症因子和细胞来促进血管生成与动脉生成，恢复缺血区的血液供应、改善组织细胞的氧和营养物质供给，才能全面的治疗缺血性血管疾病，它将成为缺血性血管疾病治疗的发展方向。     

肝癌血管生成与抗血管生成治疗的研究进展

目的 介绍肝癌血管生成的分子机理及抗血管生成在肝癌发展与治疗中的作用与意义.方法 复习相关文献资料并作综述.结果 肝癌血管生成在肝癌的发生与发展中具有重要意义,抗血管生成能有效地阻碍肝癌的发展和转移,可为临床肝癌治疗提供新的途径.结论 了解肝癌血管生成的分子机理及应用抗血管生成治疗对肝癌的防治将有积极的意义.     

膀胱癌血管生成和抗血管生成的研究进展

血管生成是肿瘤特殊生物学行为的重要过程之一。本文就成纤维细胞生长因子，血管内皮生长因子，肝细胞生长因子，胸苷磷酸化酶等若干种参与膀胱癌血管生成的促血管生长因子的最新研究进展作一综述，并探讨抗血管生成在膀胱癌治疗中的现状及应用前景。     

炎症与糖尿病肾病发生发展的关系

糖尿病肾病(DN)发病机制中除了糖脂代谢紊乱、血液动力学异常,炎症可能在DN进展中起着关键作用。炎症能引起DN,并在DN进展的整个过程中起了重要作用。目前已有学者在动物模型中应用抗炎治疗,延缓了DN的进展。     

Hypoxia--a key regulator of angiogenesis and inflammation in rheumatoid arthritis

The importance of inflammation in rheumatoid arthritis (RA) is well understood. This knowledge has resulted in the development of anti-inflammatory therapies--either broadly acting (such as steroids) or more specific approaches (such as antibodies against TNF)--with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA. However, what is less well appreciated in RA are the links between inflammation, blood-vessel formation (angiogenesis) and cellular responses to changes in oxygen tension. Inadequate oxygenation, termed hypoxia, is thought to drive the increase in synovial angiogenesis that occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This process promotes further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. This Review highlights the molecular pathways activated by hypoxia, and how these pathways might interact with inflammatory signaling to promote and maintain synovitis in RA, with a particular focus on the response of macrophages to hypoxia in the context of RA. Successful treatment of RA, for example with anti-TNF antibodies, reduces levels of proangiogenic factors, including VEGF, and leads to normalization of the vasculature. These processes emphasise the close links between hypoxia, angiogenesis and inflammation in this disease and supports the concept that angiogenesis blockade could be of therapeutic benefit in RA.     

The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm(2). Quantitative microvessel density (MVD) has been shown to provide staging and prognostic significance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative fields of similar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage. These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications.     

Ultrahigh dose gentamicin alters inflammation and angiogenesis in vivo and in vitro

Skin quality outcome after skin grafting is adversely affected by wound bed inflammation. Neomycin, gentamicin, and other aminoglycoside antibiotics are known to modulate inflammation, and topical application affords the use of higher doses than are possible to use systemically. Previous data suggest that clinically relevant doses of neomycin, but not gentamicin, may impair angiogenesis, which is critical to the durable survival of skin grafts. The role of gentamicin at ultrahigh doses compared with clinically relevant neomycin doses in regulating inflammatory expression and angiogenesis has been examined. In a porcine skin replacement excisional wound model, continuous exposure to gentamicin increased anti‐angiogenic and inflammatory expression at 7 days postgrafting. In in vitro studies, gentamicin also impaired angiogenesis in a human umbilical vein endothelial cell (HUVEC) tube formation model, increased the expression of the anti‐angiogenic gene C‐X‐C motif chemokine 10 (CXCL10) in HUVECs and macrophages, and increased pro‐inflammatory cytokine expression of macrophages in a dose‐dependent manner. Neomycin exerted similar effects in vitro at clinically relevant doses on HUVEC tube formation and macrophage pro‐inflammatory expression. CXCL10 was upregulated in macrophages, but did not exhibit a change in HUVECs with neomycin treatment. Ultrahigh doses of gentamicin and clinically relevant doses of neomycin affect inflammation and angiogenesis in in vivo and in vitro models. These findings suggest that topical administration of aminoglycosides have the potential to adversely influence early skin graft survival.     

Rapamycin prevents interstitial fibrosis in renal allografts through decreasing angiogenesis and inflammation

Rapamycin (RPM) has antiangiogenic and antiproliferative effects on cells. The aim of this study was to evaluate the mechanism of RPM as a novel antifibrotic agent by assessing its effect on interstitial fibrosis (IF). Among 60 renal transplant recipients, group 1 patients (n = 20) were treated with RPM and group 2 (n = 40), with cyclosporine. The proportions of infiltrating macrophages and lymphocytes in the interstitium were evaluated in 1-year biopsies. The microvessels were highlightened with CD34. After an initial biopsy, the development of diffuse IF over 18 months was evaluated by follow-up biopsies. The mean microvessel density (MVD) was significantly lower among group 1 (69.3 ± 16) versus group 2 (96.5 ± 30; P < .001). The proportions of macrophages and lymphocytes were lower in group 1 compared to group 2 biopsies (P < .001 for both). Fourteen (35%) group 2 and only 2 (10%) group 1 cases developed IF over 18 months (P < .05). The mean MVD in the initial biopsy was 75.6 ± 18 in cases that did not versus 120 ± 28 among those who did develop IF (P < .001). The amount of interstitial inflammation was greater among patients who did compared with cases who did not develop IF (P < .01). The overall 1-, 3-, and 5-year graft survival rates for group 1 were 95%, 95%, and 89% versus 95%, 65%, and 45% for group 2 patients, respectively (P < .001). RPM-treated patients showed a lower incidence of diffuse IF, which can be explained by antiproliferative and antiangiogenic effects of RPM. In conclusion, RPM therapy displayed an independently positive impact on long-term graft survival.     

促血管生成素在肝癌组织中的表达与肝癌新生血管形成及转移的关系

目的　观察促血管生成素 (angiopoietin)在肝细胞癌组织中的表达 ,探讨其临床意义。方法　采用原位分子杂交和免疫组织化学染色方法检测两种促血管生成素Angiopoietin 1(Ang 1)、Angiopoietin 2 (Ang 2 )以及血管平滑肌激动蛋白 (α smoothmuscleactin ,α SMA)在正常肝脏组织和肝细胞癌组织中的表达。结果　Ang 1mRNA在正常肝脏和肝癌组织中都有表达 ,肝癌组织和癌旁组织 (5 6± 6 /HP)以及正常肝脏 (6 7± 11/HP)之间差异没有显著意义 (t=3 2 14 ,P =0 12 6 )。Ang 2mRNA在正常肝脏不表达 ,肝癌组织中阳性表达 (阳性细胞数为 32± 8/HP)。Ang 2集中于癌灶边缘、血管周围。肝癌组织中微血管密度 (15± 2 /HP)和新生血管的数量 (9± 3/HP)明显高于正常肝脏(分别为 5± 1/HP和阴性 ) ,Ang 2的表达随肝癌组织的病理学分级、有无转移以及新生血管数和微血管密度而增加 (t=2 714 ,P =0 0 31)。结论　促血管生成素在肝癌的新生血管形成和转移过程中可能起到一定作用。Ang 2可能参与了肝癌的新生血管形成。     

Caveolin-1在肝细胞癌表达及与肿瘤血管生成的关系

目的：探讨caveolin-1与肝细胞癌（HCC）侵袭转移的关系及其可能的机制。方法：应用实时PCR方法检测伴肝内转移的 HCC组织、癌旁组织、肝硬化组织、正常肝组织中 caveolin-1 mRNA的表达;用Western blot方法检测伴肝内转移的 HCC组织、癌旁组织中caveolin-1蛋白的表达;用免疫组化方法检测75例HCC组织中caveolin-1,血管内皮生长因子（VEGF）,CD34,α-平滑肌肌动蛋白（α-SMA）的表达,分析caveolin-1,VEGF的表达以及肿瘤微血管密度（MVD）,非成对动脉（UA）计数与临床病理因素的关系。结果：在伴肝内转移的HCC组织中,caveolin-1 mRNA表达明显高于癌旁组织、肝硬化组织、正常肝组织（均P<0.05）,其蛋白表达明显高于癌旁组织;caveolin-1表达水平的升高与肿瘤转移有关（P<0.05）,且caveolin-1的表达与VEGF表达及MVD和UA计数呈正相关（r=0.293,P=0.011;r=0.361,P=0.001;r=0.388,P=0.001）。结论：caveolin-1表达升高促进HCC的侵袭转移,其机制可能是通过诱导HCC表达VEGF,促进肿瘤新生血管生成而实现的。