血栓栓塞性疾病包含动脉血栓栓塞性疾病、静脉血栓栓塞性疾病及微血管血栓栓塞(如弥漫性血管内凝血、血栓性血小板减少性紫癜).许多研究表明,血栓栓塞性疾病与血管性血友病因子裂解酶(即ADAMTS-13)活性的改变有着密切的关系.ADAMTS13主要由血管内皮细胞、肝脏星状细胞、骨骼肌细胞等细胞合成和分泌.本文就血栓栓塞性疾病与ADAMTS-13相关性方面的研究进展作一综述.

Thromboembolism encompasses arterial thromboembolism,venous thromboembolism,and microvascular thromboembolism such as disseminated intravascular coagulation,thrombotic thrombocytopenic purpura.Many studies show that there is close association between thromboembolism and change on activity of yon Willebrand factor-cleaving protease (ADAMTS-13).ADAMTS-13 is synthesized and secreted by vascular endothelial cells,hepatic stellate cells,and other cells.This paper is aimed to review progress of the association between thromboembolism and ADAMTS-13.

目的探讨抗血管性血友病因子(vWF)抗体在特发性血栓性血小板减少性紫癜(TTP)发病中的意义。方法选择广西壮族自治区人民医院2010年1月至2013年6月间收治的特发性TTP患者28例,同时选取同期门诊体检健康者30例作为健康对照组,检测两组对象血浆抗血管性血友病因子裂解酶(ADAMTS13)和vWF相关指标。结果 (1)28例特发性TTP患者中有3例患者vWF抗体阳性(vWF抗体阳性组),其余患者vWF抗体阴性(vWF抗体阴性组)。vWF抗体阳性组血浆ADAMTS13抗体均为阴性。(2)vWF抗体阳性组血浆ADAMTS13含量明显低于vWF抗体阴性组和健康对照组,3组血浆ADAMTS13水平比较差异有统计学意义(P0.01)。vWF抗体阳性组血浆vWF抗体A值明显高于vWF抗体阴性组和健康对照组比较,差异有统计学意义(P0.01)。(3)28例特发性TTP经过血浆置换(PE)后ADAMTS13抗原含量明显升高,vWF抗体A值明显降低(P0.05)。结论 vWF抗体在特发性TTP发病中起到重要的作用,vWF抗体可能通过影响患者血浆ADAMTS13,促进vWF复合物形成,影响疾病发生。

Objective To discuss the effect of von willebrand factor (vWF) antibody on idiopathic thrombotic thrombocytopenic purpura(TTP) .Methods 28 cases of idiopathic thrombotic thrombocytopenic purpura were selected in our hospital from January 2011 to June 2013 ,and 30 healthy persons as control group ,ADAMTS13 and vWF of two groups were detected .Results 3 cases of patients were detected with positive vWF antibody ,vWF antibody negative in the remaining patients .3 patients with positive vWF antibody ADAMTS13 antibodies were negative ,ADAMTS13 levels were lower than the normal value .The levels of ADAMTS13 in vWF antibody positive patients was significantly lower than that of vWF antibody negative patients and the control group ,(P<0 .01) .vWF antibody positive patients plasma vWF antibody A was higher than vWF antibody negative and the control group (P<0 .01) .In idiopathic TTP after PE ADAMTS13 antigen increased significantly ,vWF antibody and A levels decreased significantly (P<0 .05) .C

目的 探讨在炎症因子白细胞介素（IL）-1β刺激下,骨形态发生蛋白（BMP）-7对小鼠关节软骨细胞合成表型及分解表型的作用,为BMP-7用于骨关节炎（OA）治疗提供科学证据。方法 将原代培养的小鼠关节软骨细胞分为6组,对照组包括未加处理的空白组、IL-1β（5 ng/ml）组,实验组包括3个浓度梯度（10、50、200 ng/ml）BMP-7分别与IL-1β（5 ng/ml）共作用组、单独BMP-7（200 ng/ml）组,作用时间为24 h。用逆转录-定量聚合酶链反应（RT-qPCR）检测Ⅱ型胶原（ColⅡ）、聚集蛋白聚糖（aggrecan）、Y染色体性别决定结构域转录因子（Sox）9等合成基因及基质金属蛋白酶（MMP）-3、MMP-13、含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶（ADAMTS）-5等分解基因表达变化。再用酶联免疫吸附试验（ELISA）验证MMP-3、MMP-13蛋白表达水平。结果 在IL-1β作用下,软骨细胞特异合成基因显著下调并表达分解表型。添加BMP-7后,受抑制的合成基因得到一定程度恢复,MMP-3、MMP-13、ADAMTS-5等蛋白酶表达量明显减少,其中200 ng/ml BMP-7的促合成、抑分解作用最佳。单独BMP-7作用于软骨细胞会上调aggrecan表达,但不影响ColⅡ和Sox9表达。结论 BMP-7对OA的治疗作用与BMP-7调控炎症环境中软骨细胞

Objective To investigate the effects of bone morphogenetic protein (BMP)-7 on anabolic and catabolic phenotypes of murine chondrocytes treated with interleukin (IL)-1βand supply scientific data for osteoarthritis (OA)treatment using BMP-7.Methods Primary cultured murine chondrocytes were divided into six groups:nontreatment group and IL-1β(5 ng/ml)group as control groups,groups of different concentrations of BMP-7 (10,50,200 ng/ml)mixed with IL-1β(5 ng/ml)and BMP-7 (200 ng/ml)only group as experiment groups.After 24 h treatment,reverse transcription-quantitative polymerase chain reaction (RT-qPCR)were conducted to determine the expression levels of anabolic factors,including type Ⅱcol agen (ColⅡ),aggrecan and SRY-related high mobility group-box (Sox)9,and catabolic factors,including matrix metal oproteinase (MMP)-3,MMP-13 and a disintegrin and metal oproteinase with thrombospondin motifs (ADAMTS)-5.The protein levels of MMP-3 and MMP-13 in cel culture medium were measure

目的检测IL-1β对ATDC5成软骨分化细胞miR-455-3p表达的影响,探索miR-455-3p在骨关节炎中的作用。方法诱导ATDC5细胞成软骨分化后,予10 ng/ml的IL-1β刺激,在刺激4、12、24、48 h时应用实时荧光定量PCR检测miR-455-3p、C/EBPβ和软骨特征性标记物的表达情况;并利用抑制剂IKK-NBD阻断NF-κB通路后,应用实时荧光定量PCR检测IL-1β作用下miR-455-3p的表达水平。结果在IL-1β作用下的ATDC5成软骨分化细胞中miR-455-3p、C/EBPβ和软骨退变标记物(MMP13、ADAMTS5)均上调,而软骨基质合成标记物(ACAN、COL2A1、SOX9)则下调,且后期更为明显;而IKK-NBD可抑制IL-1β诱导的miR-455-3p表达。结论 IL-1β可上调ATDC5成软骨分化细胞miR-455-3p的表达水平,且受NF-κB通路的调节。

Objective To investigate the effects of IL-1 beta ( IL-1β) on the expression of miR-455-3p in the differentiated ATDC5 cells.Methods After chondrogenic differentiation , ATDC5 cells were treated with 10ng/ml recombinant murine IL-1βfor different time length.Additionally, a NF-kappaB inhibitor IKK-NBD was added to the cell culture before the IL-1βtreatment.The expression of miR-455-3p, C/EBP βand the genes related to cartilage were detected by quantitative real-time PCR.ResultsThe IL-1β-treat differentiated ATDC5 cells increased the expression of miR-455-3p, C/EBP β, MMP13 and ADAMTS5, while decreased the expression of ACAN , COL2A1 and SOX9 especially in the late stage. IL-1β-induced up-regulation of miR-455-3p was inhibited by IKK-NBD.Conclusion The expression of miR-455-3p in the differentiated ATDC5 cells can be induced by IL-1βand NF-kappa B is involved in the up-regulation.