肱骨干骨折骨不连的医源性原因及治疗

<正>肱骨干骨折骨不连在临床上并非少见,其原因甚多,其中由于医源性处理不妥导致延迟愈合及骨不连发生不可忽视。笔者通过对1999～2007年一组肱骨骨不连患者资料回顾性研究发现:内、外固定失当等原因为骨不连的重要原因之一。     

骨折后骨不连治疗分析

目的总结陈旧性骨折后骨不连的治疗经验,分析骨不连的病因,评价手术治疗的有效性。方法回顾性对济源钢铁（集团）有限公司职工医院骨科从2010年7月—2013年7月手术治疗的14例骨不连患者进行分析,均采用锁定加压钢板加自体骨移植的治疗方法。综合评价骨折骨折愈合率、手术并发症、临床效果。结果本组14例患者,经过术后随访,患者均达到骨性愈合。随访时间3～24个月,骨折愈合时间4～12个月,平均7.1个月。其中12例临近关节功能得到明显改善,另有2例临近关节仍存在活动障碍,无内固定失败等。结论骨不连是骨折切开复位内固定术后常见并发症,骨折部位、骨折类型的不同以及术后发生感染均是引起骨折后骨不连的重要原因。锁定加压钢板内固定加自体骨移植技术是治疗陈旧性骨不连较为有效的方法。     

骨折内固定术后骨不连10例分析

骨折内固定后因不同原因造成固定失败、骨迟缓愈合、骨不连,临床上常见,自1998年至2006年共收集10例,其中9例采取扩创、髓腔减压、植骨、予以牢靠的内固定等治疗,全部得到随访,现分析如下.     

骨形成蛋白7及骨形成蛋白受体IA在脑胶质瘤中的表达

目的 探讨骨形成蛋白7（BMP-7）及骨形成蛋白受体IA（BMPR-IA）在胶质瘤中的表达及其与预后的相关性。方法 应用免疫组织化学方法检测60例脑胶质瘤标本（Ⅰ型8例、Ⅱ型24例、Ⅲ型16例、Ⅳ型12例）和5例正常脑组织标本BMP-7和BMPRIA表达情况,对表达丰度进行半定量差异分析。结果 BMP-7和BMPR-IA在脑胶质瘤中表达丰度均随肿瘤恶性程度增加而增加。肿瘤1年生存率与BMP-7和BMPR-IA表达旱负相关。Ⅰ、Ⅱ、Ⅲ和Ⅳ型组的1年生存率分别为100．0％、66．6％、43．7％和25．0％。结论 BMP-7和BMPRIA在脑胶质瘤中表达丰度随着恶性程度增加而增加,且与预后呈负相关,提示BMP-7和BMPR-IA与脑胶质瘤的形成、生物学行为相关。     

应用SOD后实验性骨痂超微结构观察及体视觉分析

为探讨超氧化物歧化酶（ＳＯＤ）对实验性骨折愈合的影响，结合实验性骨折大鼠静脉注射ＳＯＤ，透射电镜观察实验性骨痂组织、细胞的超微结构改变，并用微机图像处理系统对骨痂骨系细胞进行立体定量分析。结果显示：ＳＯＤ可使①早期骨痂内毛细血管含量增加；②骨生成细胞增殖并向成骨细胞转化，成骨细胞数量增加，体积较大；③成髓细胞、成纤维细胞和破骨细胞功能活跃，骨痂的骨化、改建以及塑建速率加快。结论：ＳＯＤ可作为促进骨     

骨泌肽治疗骨折延迟愈合骨不连临床观察

目的：探讨骨泌肽在骨折延迟愈合和骨不连临床应用及疗效。方法：1998年3月—2002年10月采用骨泌肽经皮注射治疗长骨骨折延迟愈合26例，骨不连16例，每月拍X片对照。结果：42例均行跟踪观察随访4—12个月，平均8个月，延迟愈合26例中愈合25例，愈合率96％。骨不连接16例中愈合14例，愈合率87％，愈合时间3—6个月，平均4个月。结论：骨泌肽经皮注射治疗长骨骨折延迟愈合骨不连接具有临床疗效确定，患痛苦小，医疗费用低，副作用小的特点。     

股骨远端骨折术后骨不连的原因及处理方法

骨折不连接(non-union of fracture NUF)也称骨折不愈合,是指骨折在其愈合过程中超过正常期限,X线片上出现骨髓腔封闭,骨折端硬化和假关节形成,继续固定仍不能连接者.     

16例肱骨干骨折术后骨不连原因分析

目的探讨经手术治疗的肱骨干骨折发生骨不连的原因。方法对16例肱骨干骨折术后骨不连患者的骨折类型、手术方式、内固定材料、术后康复治疗等综合分析来判断骨不连的原因。结果16例患者均存在有不同程度的医源性因素。结论术中严格遵循生物力学及生物学的基本原则,术后合理有效地康复训练是防止骨不连的关键。     

Stimulatory effects of eicosanoids on ovarian angiogenesis in early luteal phase in cyclooxygenase-2 inhibitor-treated rats

Our previous study demonstrated that impaired ovarian vasculature is responsible for the decrease in serum progesterone observed in cyclooxygenase (COX)-2 inhibitor-treated rats. To explore the role of arachidonic acid metabolites in the formation of the corpus luteum, we determined in the present study the effects of prostaglandin (PG) and thromboxane (TX) receptor agonists together with vascular endothelial growth factor (VEGF) on progesterone secretion and angiogenesis in the newly formed corpus luteum in NS-398 (a selective inhibitor of COX-2)-treated rats. Uterine injection of PGE2 or U-46619 (TXA2 receptor agonist) prevented decreased levels of serum progesterone and ovarian hemoglobin, an indicator of amounts of vasculature in NS-398-treated rats. Luteal capillary vessel establishment was inhibited by NS-398, as determined by histological examination of ovarian vascular plexuses, while administration of PGE2 reversed the effect. VEGF enhanced the levels of serum progesterone and ovarian hemoglobin, and increased the density of ovarian capillaries. However, VEGF-induced angiogenesis was inhibited by NS-398 treatment. These results suggest that PGE2 and TXA2 stimulate angiogenesis in the newly formed corpus luteum and that there is a possibility that these eicosanoids are involved in VEGF-induced progesterone production and the increase in luteal blood flow.     

重组人VEGF和前列腺素E1对移植脂肪早期血管生成的作用

目的探讨重组人血管内皮细胞生长因子165（hVEGF165基因质粒转染移植脂肪组织和脂微球化前列腺素E1（Lipo—PGE1）局部应用对移植脂肪颗粒早期血管生成的作用。方法在颗粒脂肪移植的动物模型中,分别应用PCD-VEGF165质粒、Lipo—PGE1、PCD-VEGF165质粒＋Lipo—PGE1。Western blot检测实验组和对照组移植组织的VEGF表达,免疫组化法测定各组移植组织的微血管密度值。结果各实验组组织中VEGF蛋白表达量及微血管密度值明显高于对照组。结论VEGF165基因质粒能在移植脂肪组织中表达外源性VEGF蛋白,诱导移植脂肪血管的新生,Lipo-PGE1能有效促进移植脂肪早期血管生成,VEGF165基因质粒和Lipo—PGE1有协同作用。     

组蛋白去乙酰化酶抑制剂抗血管新生机制的体内研究

目的 探讨组蛋白去乙酰化酶(HDAC)抑制剂对白血病细胞移植瘤血管新生的影响及其机制.方法 12只裸鼠均分为对照组和丙戊酸钠(VPA)用药组.建立Kasumi-1细胞裸鼠移植瘤模型,应用HDAC抑制剂VPA体内用药.RT-PCR和免疫组化检测血管内皮生长因子(VEGF)及其受体(VEGFR) mRNA或蛋白的表达;染色质免疫共沉淀法检测VEGF基因启动子区域染色质内组蛋白H3乙酰化程度的变化.结果 与对照组比较,VPA用药组VEGF及VEGFR2 mRNA和蛋白表达水平明显减少,启动子区域染色质内组蛋白H3的乙酰化程度明显升高.结论 VPA作为HDAC抑制剂,通过提高组蛋白的乙酰化程度,进而抑制血管新生相关因子及受体的表达,阻碍白血病的血管新生.     

血管生长刺激因子在肝癌中的表达及肿瘤组织微血管密度和预后的关系

目的 :研究临床指标、血管生成刺激因子、组织微血管密度与患者预后的关系。方法 :用免疫组化的方法分别检测71例肝癌组织中VEGF、PCNA(增殖细胞核抗原 )、EGFR ,bFGF、PD -ECGF的表达 ,利用CD34单克隆抗体检测肝癌组织的新生血管 ,400倍光学显微镜下计算每个视野新生血管密度。结果 :(1)免疫组化表达 :71例肝癌组织中VEGF,PD -ECGF ,EGFR,bFGF,PCNA的阳性表达率分别为 :60.4 %、73.2 %、54.9%、20.1%、90 % ;(2)微血管密度 (MVD)表达 :根据MVD中位值分组 (血管数≤40为1,41～79为2 ,>80为3) ,(以中位值分组 ,就只能分为2组 )与MVD明显相关有VEGF(P=0.003) ,PD -ECGF(P=0.001) ,EGFR(P=0.004) ,MVD与bFGF和PCNA的表达无关 ;(3)肝癌患者的癌组织中的VEGF、微血管密度和有无微血管癌栓与患者的术后复发有关。多因素分析显示微血管癌栓、VEGF和肿瘤组织微血管密度影响患者的无瘤生存时间。结论 :肝癌组织中的VEGF、微血管密度和有无微小癌栓影响患者的无瘤生存期 ,可作为提示手术患者预后的指标。     

黄芪注射液促进鸡胚绒毛尿囊膜血管生成的实验研究

目的:探讨黄芪注射液对鸡胚绒毛尿囊膜(chorioallantoicmembrane,CAM)血管生成的影响。方法:种蛋随机分为5组,孵育7d后,将高、中、低剂量黄芪注射液穴Astragalusmembranaceusinjec鄄tion,AMI雪及生理盐水(NS)、成纤维细胞生长因子(EGF)对照品分别加于CAM表面的载体上,作用后制备CAM标本,解剖显微镜下计数新生血管数目。结果:黄芪注射液具有明显的促进鸡胚绒毛尿囊膜血管生成的作用,与NS阴性对照组相比有显著性差异(P﹤0.05),但药效低于EGF阳性对照组(P﹤0.05)。结论:黄芪注射液可促进鸡胚绒毛尿囊膜血管生成。     

Inhibition of in vivo angiogenesis by N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine

N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from the flesh fly, inhibits human tumor growth in the nude mice model; however, the mechanism of its action is unclear. The in vivo antitumor effect includes the inhibition of tumor cell proliferation and suppression of angiogenesis. Angiogenesis is essential for tumor growth in vivo. In this study, we examined whether 5-S-GAD inhibits tumor cell-induced angiogenesis by performing the mouse dorsal air sac assay. We found that intraperitoneal administration of 5-S-GAD inhibited the angiogenesis induced by S180 mouse sarcoma cells. Furthermore, 5-S-GAD also inhibited vascular endothelial growth factor-induced angiogenesis in the Matrigel plug assay and embryonic angiogenesis in the chick embryo chorioallantoic membrane assay. However, 5-S-GAD did not show any effect on the proliferation, migration, and tube formation of vascular endothelial cells. These results provide the first evidence that a bioactive substance derived from the flesh fly has antiangiogenic activity in vivo, although the mechanisms involved could not be explained.     

Formononetin promotes early fracture healing through stimulating angiogenesis by up-regulating VEGFR-2/Flk-1 in a rat fracture model

Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague–Dawley rats. A 20 µg/kg or 200 µg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.     

Inhibition of angiogenesis and tumor growth by beta and gamma-secretase inhibitors

The involvement of beta-secretase and gamma-secretase in producing the beta-amyloid component of senile plaques found in the brain of Alzheimer's patients has fueled a major research effort to design selective inhibitors of these proteases. Interestingly, gamma-secretase cleaves several proteins including Notch, E-cadherin, CD44 and ErbB-4 (erythroblastic leukemia viral oncogene homolog 4), which are important modulators of angiogenesis. The beta-amyloid precursor protein, which is cleaved by beta-secretase and gamma-secretase to produce beta-amyloid, is highly expressed in the endothelium of neoforming vessels suggesting that it might play a role during angiogenesis. These data prompted us to explore the effects of beta and gamma-secretase inhibitors of different structures on angiogenesis and tumor growth. Both the gamma and beta-secretase inhibitors tested reduce endothelial cell proliferation without inducing cellular toxicity, suppress the formation of capillary structures in vitro and oppose the sprouting of microvessel outgrowths in the rat aortic ring model of angiogenesis. Moreover, they potently inhibit the growth and vascularization of human glioblastoma and human lung adenocarcinoma tumors xenotransplanted into nude mice. Altogether these data suggest that the gamma and beta-secretases play an essential role during angiogenesis and that inhibitors of the beta and gamma-secretases may constitute new classes of anti-angiogenic and anti-tumoral compounds.     

血管形成素-1重组腺病毒对兔实验性心肌梗死治疗作用的研究

目的　研究心肌内直接注射血管形成素 1(Ang 1)重组腺病毒促进血管生长的作用及对心肌梗死范围的影响。方法　用硝基四氮唑蓝大体标本染色观测血管形成素 1对高位双重结扎兔冠状动脉前降支后造成的急性心肌梗死范围的影响 ,并用免疫组化方法观察了血管生长情况。 48只雄性新西兰白兔随机分为实验组、单纯培养基 (DMEM)组与半乳糖苷酶Z(LacZ)重组腺病毒组 ,分别于冠状动脉结扎后心肌内直接注射血管形成素 1重组腺病毒 ,DMEM与LacZ重组腺病毒。第 14天与第 2 8天各组分别处死 8只 ,以观测心肌梗死与及血管新生情况。结果　在结扎冠状动脉前降支后 14天 ,实验组与对照组梗死心肌范围及新生毛细血管数目均无明显差异 ,术后 2 8天的结果显示实验组心肌梗死范围显著小于对照组 ,而新生毛细血管密度明显高于对照组 (P <0 0 1)。结论　血管形成素 1能促进兔实验性心肌梗死区新生血管形成 ,减轻心肌梗死程度