Two faces of high-molecular-weight kininogen (HK) in angiogenesis: bradykinin turns it on and cleaved HK (HKa) turns it off.

High-molecular-weight kininogen (HK) is a plasma protein that possesses multiple physiological functions. Originally identified as a precursor of bradykinin, a bioactive peptide that regulates many cardiovascular processes, it is now recognized that HK plays important roles in fibrinolysis, thrombosis, and inflammation. HK binds to endothelial cells where it can be cleaved by plasma kallikrein to release bradykinin (BK). The remaining portion of the molecule, cleaved HK, is designated cleaved high-molecular-weight kininogen or HKa. While BK has been intensively studied, the physiological implication of the generation of HKa is not clear. Recent studies have revealed that HKa inhibits angiogenesis while BK promotes angiogenesis. These findings represent novel functions of the kallikrein-kinin system that have not yet been fully appreciated. In this review, we will briefly discuss the recent progress in the studies of the molecular mechanisms that mediate the antiangiogenic effect of HKa and the proangiogenic activity of BK.     

鬼臼乙叉甙对SHG-44胶质瘤细胞表达β-1,4-半乳糖基转移酶Ⅴ后粘附相关分子表达的影响

目的　研究人脑星形胶质细胞瘤SHG 4 4细胞表达 (β 1,4 半乳糖基转移酶Ⅴ (beta 1,4 galactosyltransferaseⅤ ,β 1,4 GalTⅤ )后对化疗药物敏感性的影响 ,分析鬼臼乙叉甙 (VP16 )处理表达 β 1,4 半乳糖基转移酶Ⅴ的SHG 4 4细胞后其细胞粘附作用相关因子水平的变化。方法　用 12 0 μmol/L的VP16处理转染了正义、反义 β 1,4 GalTⅤ和空载体的SHG 4 4细胞 2 4h后 ,采用westernblot检测整合蛋白 β1表达变化及局部粘着斑激酶 (focaladhesionkinase,FAK)的蛋白水平和FAK的酪氨酸磷酸化水平。结果　在未经VP16处理的 3株SHG 4 4细胞中 ,FAK的蛋白水平没有明显改变 ,而整合蛋白 β1的蛋白表达在转正义 β 1,4 GalTⅤ的细胞中最高 ;经VP16处理后 ,SHG 4 4细胞中整合蛋白β1的表达水平增高 ,FAK及其磷酸化水平下降。但整合蛋白β1,FAK及其磷酸化水平随细胞中 β 1,4 GalTⅤ表达水平不同而变化。 结论　VP16处理对表达不同水平的β 1,4 GalT Ⅴ的SHG 4 4胶质瘤细胞的粘附影响有所不同 ,提示胶质瘤表达 β 1,4 GalTⅤ不仅与肿瘤的恶性行为有关 ,而且与肿瘤的化疗敏感性有关。     

持续闭式灌洗预防椎板切除后硬膜粘连

目的 观察持续闭式灌洗预防椎板切除后硬膜粘连的效果。方法 选成年健康新西兰大白兔 30 只,每只兔的背部做两处切口,分别切除L2 和L6 棘突、椎板,显露硬膜囊,其中一处直接缝合,作为对照组;另一处持续灌洗 72 h,作为冲洗组。术后4周、8周、12周取样行大体和光镜检查,12周样本增加透射电镜检查及计算机图像分析。结果 术后 4 周和 8 周样本见对照组硬膜外腔被大量瘢痕组织填充,直达肌筋膜层,瘢痕与硬膜及周围肌肉组织粘连紧密,难以剥离;冲洗组见硬膜与肌肉之间为膜性物、浸润脂肪或少量瘢痕,与硬膜无粘连或部分粘连,易于钝性分离。术后 12 周样本见对照组硬膜外瘢痕致密而广泛,与硬膜紧密粘连,难以区分;冲洗组硬膜外瘢痕形成少而疏松,与硬膜轻度粘连或无粘连,与对照组存在显著性差异( P <0.05)。透射电镜下见,对照组硬膜外组织为致密瘢痕组织;冲洗组主要为脂肪组织,脂肪细胞间夹杂少量胶原纤维。结论 兔椎板切除后持续生理盐水灌洗72 h可有效防止硬膜粘连     

厄贝沙坦对SHR血浆sICAM-1浓度及主动脉VCAM-1表达的影响

目的 探讨厄贝沙坦对自发性高血压大鼠（SHR）血浆可溶性细胞间黏附分子-1（sICAM-1）浓度及主动脉血管细胞黏附分子-1（VCAM-1）表达的影响及其意义。方法 20只12周龄雄性SHR随机分为SHR对照组10只，SHR治疗组10只，予以厄贝沙坦灌胃，同时选取10只同周龄的雄性Wistar-Kyoto大鼠（WKY）作为对照。给药8周后采用夹心酶联免疫吸附法（ELISA法）测定血浆sICAM-1浓度和免疫组织化学染色法测定主动脉VCAM-1表达的阳性率。结果 与WKY大鼠比较，SHR对照组血浆sICAM-1浓度水平和主动脉VCAM-1表达的阳性率明显增高（P〈0．01）；SHR治疗组血浆sICAM-1浓度和主动脉VCAM-1表达明显低于SHR对照组（P〈0．01），且SHR治疗组血浆sICAM-1浓度与WKY组比较无差异（P〉0．05）。结论 厄贝沙坦具有降低SHR血浆sICAM-1浓度及主动脉VCAM-1表达作用，厄贝沙坦在发挥降压作用的同时，可减轻血管内皮细胞损伤，检测血浆sICAM-1的水平可能成为监测高血压病的指征。     

FRK通过FAK信号通路抑制脑胶质瘤细胞迁移与侵袭作用的研究

目的研究酪氨酸相关激酶(fyn-related kinase,FRK)是否通过粘着斑激酶(focal adhesion kinase,FAK)信号通路抑制脑胶质瘤细胞的迁移和侵袭。方法采用Western blot(WB)检测FRK质粒的转染效果,细胞划痕和Transwell侵袭实验检测过表达FRK及下调FAK对胶质瘤U251细胞迁移和侵袭能力的影响;WB检测过表达FRK对FAK、P-FAK蛋白水平的影响以及下调FAK对FRK蛋白水平的影响。结果FRK质粒转染成功。过表达FRK后胶质瘤U251细胞的迁移与侵袭能力下降。FAK siRNA干扰效率达到70%,下调FAK后胶质瘤U251细胞的迁移与侵袭能力下降。过表达FRK后P-FAK的蛋白水平明显下降,而FAK蛋白水平无明显变化,下调FAK对FRK的蛋白水平无明显影响。结论 FRK可能通过抑制FAK的磷酸化来调控胶质瘤的侵袭与迁移。     

Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.     

子宫内膜异位症的分子病因学研究现状

子宫内膜异位症(EMS)是子宫内膜腺体和基质种植于子宫以外的一种雌激素依赖性疾病,是引起该病患者盆腔疼痛和不孕的常见因素。EMS的发病机制迄今尚未完全阐明,是妇产科临床和基础研究的热点。目前研究认为,EMS发病的分子机制不纯粹是某一生物学特征异常,尚涉及腹膜侵袭、血管形成、细胞凋亡、细胞黏附及自噬等方面,并且某一信号通路异常,参与EMS发病过程的各个环节,而涉及整个通路调控网络异常。笔者拟从腹膜的侵袭、血管形成、细胞凋亡、细胞黏附、自噬等方面,对EMS的分子病因学最新研究进展进行阐述。     

羊膜移植在宫腔镜下宫腔黏连分离术后预防宫腔黏连复发中的有效性和安全性

目的探讨羊膜移植对预防中、重度宫腔黏连(IUA)患者行宫腔镜下宫腔黏连分离术(TCRA)后黏连复发的有效性与安全性。 方法选择2016年12月至2017年8月,在武汉大学人民医院生殖中心因中、重度IUA行TCRA的121例患者为研究对象。根据手术日为单、双日,将其分为2组,A组(n＝76)行羊膜移植,B组(n＝45)为常规治疗组[放置宫内节育器(IUD)和可吸收生物医用膜],比较2组患者一般临床资料及疗效(宫腔恢复情况、月经量改变、术后子宫内膜厚度)和术后不良反应率等。采用成组t检验,对2组患者年龄、孕次、子宫内膜厚度进行统计学比较。采用Wilcoxon秩和检验,对2组患者人体质量指数(BMI)、病程等进行统计学分析。采用χ²检验、连续性校正χ²检验或者Fisher确切概率法,对TCRA前月经异常情况构成比、IUA程度构成比、宫腔恢复率、月经量改善率、不良反应率等进行分析。本研究遵循的程序符合武汉大学人民医院医学伦理委员会所制定的伦理学标准,得到该委员会批准(批准文号：WDRY2016-Q007),所有受试者均签署临床研究知情同意书。 结果①2组患者的年龄、孕次、BMI、病程、TCRA前月经异常情况构成比及IUA程度构成比比较,差异均无统计学意义(P>0.05)。②2组TCRA疗效评价如下。A组患者的宫腔恢复率(84.2%,64/76)显著高于B组(64.4%,29/45),月经量改善率(75.0%,57/76)明显高于B组(37.8%,17/45),术后子宫内膜厚度为[(4.2±1.6) mm],亦明显高于B组的(3.6±1.5) mm,并且上述指标比较,差异均有统计学意义(χ²＝4.367、16.485、2.168,P＝0.037、<0.001、＝0.033)。③2组患者中,无一例患者发生水中毒、子宫穿孔等严重并发症。此外,2组患者术后不良反应,如月经间期反复阴道不规则出血发生率、阴道分泌物异常发生率、腹痛发生率、外阴瘙痒发生率比较,差异均无统计学意义(P>0.05)。 结论羊膜移植为IUA患者TCRA后预防黏连复发的有效方法之一。但是,该方法的远期安全性仍然需要大样本、随机对照试验进一步证实。     

细胞间黏附分子-1和P-选择素在鼻息肉中的表达

目的:揭示细胞间黏附分子-1(ICAM-1,CD54)和P-选择素(CD62p)在鼻息肉发病机制中的作用.方法:收集鼻息内标本32例,炎性鼻甲黏膜11例,正常鼻黏膜12例作对照,应用FACScan流式细胞仪测定不同标本内表达这两种黏附分子的阳性细胞数量.结果:鼻息肉和炎性鼻甲黏膜ICAM-1和P-选择素的细胞阳性率均明显高于正常鼻黏膜(P＜0.001);鼻息肉和炎性鼻甲黏膜之间ICAM-1和P-选择素的细胞阳性率差异无显著性(P＞0.05);ICAM-1和P-选择素在鼻息肉中的表达有正相关关系(r=0.900 1,P＜0.001).结论:ICAM-1和P-选择素在鼻炎和鼻息肉发病过程中都起了重要作用,在鼻息肉中二者表达有一致性.