血清骨标志物与2 型糖尿病患者 心血管疾病风险的关系

目的 评估2 型糖尿病（T2DM）患者中6 种骨标志物（骨钙蛋白、骨桥蛋白、骨粘连蛋白、骨 保护素、碱性磷酸酶和骨硬化蛋白）水平是否与心血管疾病（CVD）风险相关。方法 选取2015 年9 月— 2018 年12 月蚌埠医学院第一附属医院收治的T2DM 患者200 例,其中100 例在2 年的随访过程中出现了 CVD。根据随访期间是否发生CVD 分为CVD 组和无CVD 组,每组100 例。用多重试剂盒法测量血清中 6 种骨标志物,使用多因素Logistic 回归分析评估骨标志物与CVD 风险的关系。结果 CVD 组年龄、糖尿病 病程、骨钙蛋白、骨桥蛋白、骨粘连蛋白、骨保护素、碱性磷酸酶、骨硬化蛋白水平较无CVD 组高（P <0.05）。 多因素Logistic 回归分析结果显示,较高血浆浓度的骨桥蛋白水平[Ol ^ R=5.112（95％ CI ：1.032,22.423）, P =0.000] 是T2DM 患者发生CVD 的危险因素。结论 高骨桥蛋白是T2DM 患者CVD 风险的独立危险因素, 而其他5 种骨标志物和CVD 风险无关。     

微缺氧对人结肠癌细胞HT-29血管生成能力及分泌基质金属蛋白酶2/9活性的影响

目的 观察HT-29细胞在微缺氧下的血管生成能力,检测OPN的表达和MMP-2/MMP-9的活性变化,以探讨其向恶性表型转化的潜在机制.方法 参照体内肿瘤的氧分压,建立微缺氧模型.内皮细胞小管形成试验检测体外促进新生血管形成的能力.将HT-29细胞微缺氧处理0、6、12、24和48 h,明胶酶谱分析检测分泌的MMP-2/MMP-9活性变化,RT-PCR和Western blot检测OPN的mRNA和蛋白表达.结果 微缺氧组内皮细胞形成的管状结构数为(28.5±3.6),明显多于对照组(12.4±2.8),其差异具有显著性(P<0.01).微缺氧6h,MMP-2/MMP-9活性无明显变化,随着微缺氧时间的延长,其活性逐渐上调,24h达顶峰,48 h与24 h差异无显著性.HT-29细胞在微缺氧的诱导下,其OPN mRNA和蛋白的表达趋势与MMP-2/9活性变化趋势类同.结论 微缺氧能诱导HT-29细胞促进新生血管形成,上调MMP-2/MMP-9活性而促进其向恶性表型转化.该实验检测到在微缺氧下OPN和MMP-2/MMP-9普遍上调,且时限同步.因此,笔者推测:OPN可能是微缺氧下继HIF-1α之外的另一重要调控因子,该调控因子与微缺氧诱导的恶性表型密切相关.     

过表达骨桥蛋白对游离脂肪酸诱导RIN m5f细胞凋亡的保护作用

目的通过构建骨桥蛋白过表达细胞模型,研究骨桥蛋白对游离脂肪酸诱导RINm5f细胞凋亡的保护作用。方法构建骨桥蛋白真核表达质粒,转染细胞,游离脂肪酸诱导细胞凋亡,检测游离脂肪酸作用前后对照组及过表达组骨桥蛋白及其mRNA水平,细胞凋亡水平,凋亡相关基因水平,探究骨桥蛋白对游离脂肪酸诱导的RINm5f细胞凋亡的作用。结果游离脂肪酸作用后,骨桥蛋白表达增加,过表达组较对照组,游离脂肪酸作用后细胞凋亡率降低,凋亡相关基因BAX,Bcl-2表达水平明显降低。结论骨桥蛋白对游离脂肪酸诱导的RINm5f细胞凋亡具有有效的保护作用。     

Impairment of myocardial angiogenic response in the absence of osteopontin

OBJECTIVE: Osteopontin (OPN), increased in the heart following myocardial infarction (MI), plays an important role in post-MI remodeling. Angiogenesis, an important feature of tissue repair, begins in the infarcted myocardium within 3 days post-MI. Here, the authors studied the role of OPN in myocardial angiogenesis using wild-type (WT) and OPN knockout (KO) mice. RESULTS: Measurement of angiogenic response using Griffonia simplicifolia lectin-1 (GSL-1) staining indicated reduced capillary density in the infarcted region of the OPN KO hearts as compared to WT hearts 7 and 14 days post-MI. Arteriolar density was lower in OPN KO hearts 14 days post-MI. The number of CD31 positive cells was also lower in the infarcted region of the OPN KO hearts as compared to WT hearts 14 days post-MI. In contrast, capillary and arteriolar densities in the noninfarcted regions of OPN KO and WT hearts were not significantly different. In vivo myocardial angiogenesis measured using Matrigel implantation in the left ventricular myocardium indicated significant decrease in the percentage of vessel-like areas in the OPN KO vs. WT hearts. Furthermore, in vitro Matrigel tube formation assay demonstrated a significant decrease in total tube length in cardiac microvascular endothelial cells (CMECs) isolated from OPN KO hearts as compared to CMECs from WT hearts. Treatment of OPN KO CMECs with purified OPN protein significantly increased total tube length, while bovine serum albumin had no effect. CONCLUSION: Lack of OPN impairs myocardial angiogenic response, leading to adverse remodeling post-MI.     

骨桥蛋白在心力衰竭中的作用

近期相关研究提示,骨桥蛋白与心功能不全严重程度相关,其机制与介导细胞外基质表达,肾素-血管紧张素-醛固酮系统调控相关,有望作为心力衰竭患者临床评估的新的生物化学指标。本文就骨桥蛋白的结构、功能及其与心力衰竭相关的机制和意义进行综述。     

卵巢癌中OPN、αv133和VEGF的表达与侵袭转移的关系

目的探讨骨桥蛋白（OPN）、整合素αvB3和血管内皮生长因子（VEOF）在上皮性卵巢癌（EOC）中的表达及其临床意义,寻求卵巢癌可能的肿瘤标记物。方法采用免疫组化方法,检测50例卵巢癌组织、20例卵巢良性肿瘤组织及10例正常卵巢组织标本中骨桥蛋白、整合素αvβ3和血管内皮生长因子的表达,分析它们与患者临床病理参数的关系及其之间的相互关系。结果骨桥蛋白、整合素αvβ3和血管内皮生长因子在卵巢癌组的表达率均明显高于正常组和良性肿瘤组（X^2值分别为41．302、28．544、28．848,均P〈0．05）。在晚期卵巢癌中的骨桥蛋白、整合素αvβ3和血管内皮生长因子阳性表达率均高于早期的卵巢癌（X^2值分别为7．728、23．000、9．432,均P〈0．05）;分化差卵巢癌中骨桥蛋白和整合素αvβ3阳性表达率明显高于分化好的卵巢癌（X^2值分别为6．542、12．167,均P〈0．05）;有淋巴结转移的卵巢癌中,骨桥蛋白、整合素αvβ3和血管内皮生长因子阳性表达率高于无淋巴结转移的卵巢癌（X^2值分别为6．629、13．782、4．726,均P〈0．05）。骨桥蛋白与整合素αvβ3、血管内皮生长因子在卵巢癌中的表达均显著相关（,值分别为4．973、5．821,均P〈0．05）。骨桥蛋白、整合素αvβ3和血管内皮生长因子的共表达与卵巢癌的淋巴结转移显著相关（X^2=9．343,P〈0．05）。结论骨桥蛋白、整合素αvβ3和血管内皮生长因子的过度表达可能促进了卵巢癌的浸润转移,骨桥蛋白表达与整合素αvβ3、血管内皮生长因子表达分别具有正协同作用。联合检测骨桥蛋白、整合检测骨桥蛋白、整合素αvβ和血管内皮生长因子可作为预测卵巢癌浸润转移及评价患者预后的生物学指标。     

辛伐他汀对心肌梗死后心肌骨桥蛋白表达的影响及其与心室功能的相关性

目的 在大鼠心肌梗死模型上,观察辛伐他汀是否下调OPN mRNA及蛋白表达,及其与改善大鼠心肌梗死后心室重塑和心脏功能的关系.方法 制备MI模型,予辛伐他汀干预.分为3组:Sim组、MI组及假手术组.4周后分别测定左、右心室质量指数,血流动力学指标,HE染色观察心肌组织病理学改变,运用免疫组化、RT-PCR方法检测OP...     

Heterogeneity of hepatocellular carcinoma contributes to cancer progression

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease displaying differences in angiogenesis, extracellular matrix proteins, the immune microenvironment and tumor cell populations. Additionally, genetic variations and epigenetic changes of HCC cells could lead to aberrant signaling pathways, induce cancer stem cells and enhance tumor progression. Thus, the heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.     

Endometrial Osteopontin mRNA Expression and Plasma Osteopontin Levels are Increased in Patients with Endometriosis

Problem  The aim of this study was to evaluate osteopontin (OPN) mRNA expression in eutopic endometrium and plasma OPN levels in patients with endometriosis.
Method of study  A total of 79 patients with histologically confirmed endometriosis and 43 patients without endometriosis participated in this study. OPN mRNA expression in endometrial tissues was measured by real-time quantitative polymerase chain reaction (PCR) and plasma concentrations of OPN were quantified using a specific commercial sandwich enzyme-linked immunosorbent assays (ELISA).
Results  Osteopontin mRNA expression in endometrial tissue was significantly higher in women with endometriosis than in controls ( P =  0.010). The mean plasma levels of OPN (mean ± S.E.M.) in patients with endometriosis and controls were 407.31 ± 37.80 ng/mL and 165.84 ± 19.29 ng/mL, respectively ( P  < 0.001). Receiver operating characteristic (ROC) analysis for plasma OPN revealed an area under the curve (AUC) of 0.894, with a sensitivity of 93.0%, specificity of 72.4%, positive likelihood ratio of 3.37, and negative likelihood ratio of 0.1 using a cut-off value of 167.68 ng/mL.
Conclusion  Osteopontin may be involved in the pathogenesis of endometriosis and plasma OPN may be a useful non-invasive marker for the diagnosis of endometriosis.