NLRP3炎症小体在神经血管疾病中的作用

炎症小体是多蛋白复合物,可以招募并诱导半胱氨酸天冬氨酸酶-1前体(pro-caspase-1)成为有活性的半胱氨酸天冬氨酸酶-1(caspase-1),从而促进IL-1β和IL-18成熟与释放。许多研究表明NLRP3炎症小体与缺血性脑卒中、阿兹海默症(AD)、外伤性脑损伤(TBI)、脑瘤等神经血管疾病的发生发展密切相关。本文综述了NLRP3炎症小体激活途径,并着重介绍了NLRP3炎症小体介导的在上述几种神经血管疾病中的作用,为相关研究提供了基础资料。     

主——髂动脉粥样硬化的血管内成形术的进展

主——髂动脉粥样硬化发病率较高,是介入治疗最有效的区域之一。经皮血管内成形术(PTA)是治疗主——髂动脉病变最成功的方法之一,它使大量下肢缺血跛行的患者,避免了手术之苦。本文就其应用现状进行综述。     

炎症控制下内膜新生血管在动脉硬化发生发展中的作用

目的:研究在控制炎症水平的情况下内膜新生血管在动脉硬化发生、发展中所起到的具体作用。方法:高脂饮食8周造成大鼠动脉硬化模型,使用阿司匹林抑制动脉硬化大鼠的基础炎症水平,分别给予内皮抑素和VEGF165两种不同方法处理大鼠,8周后比较血脂、胸主动脉形态学、CD31表达量。结果:模型组血脂水平与空白对照组有显著差异(P<0.05);硬化动脉内部的新生血管数量:VEGF165+阿司匹林组>单纯模型对照组>阿司匹林组>内皮抑素+阿司匹林组>空白对照组(P<0.05);阿司匹林组、内皮抑素+阿司匹林组和VEGF165+阿司匹林组的内膜面积/中膜面积比值(I A/MA)差异无显著性(P>0.05),但低于单纯模型对照组(P<0.05)。结论:仅仅依靠内膜新生血管的数量还不能够完全作为评价动脉硬化发生发展的标准,内膜新生血管的数量可能仅是炎症水平的一种外部表现形式。     

产科弥漫性血管内凝血诊治分析

产科弥漫性血管内凝血（DIC）是产科最严重并发症之一,发病急骤,病情凶险,如果抢救不及时,母婴死亡率高。近年来,由于诊断和治疗技术的不断提高,死亡率已明显下降,并且对DIC的治疗已达成许多共识,如去除病因,输新鲜血,补充凝血因子等,但肝素的应用一直有所争议。我院自2002年1月～2006年6月,共遇到并抢救产科DIC31例,现将我院近年来31例DIC资料进行回顾性分析,就产科DIC的临床特点,诊断治疗中的几个主要问题进行探讨。     

人冠状动脉硫酸乙酰肝素蛋白聚糖的分布和变化与动脉粥样硬化形成的关系

目的：观察、探讨硫酸乙酰肝素蛋白聚糖在正常及有动脉粥样硬化病变的人冠状动脉内的分布和对巨噬细胞脂质摄入的影响及其与动脉粥样硬化形成的关系。方法：应用免疫组化染色观察正常和动脉粥样硬化病变的人冠状动脉内硫酸乙酰肝素蛋白聚糖的分布;应用酶－荧光法,检测培养的巨噬细胞内胆固醇含量。结果：（１）硫酸乙酰肝素蛋白聚糖主要分布于正常冠状动脉内膜近腔面的１／３处,多定位于内皮基底膜及内膜细胞的细胞膜周围;于动脉粥样硬化病变（脂纹及斑块）内其分布密度下降,尤其是在病变深层的泡沫细胞周围分布稀少。（２）硫酸乙酰肝素蛋白聚糖能抑制巨噬细胞内脂质的聚集。结论：动脉内膜中硫酸乙酰肝素蛋白聚糖分布的减少可能与巨噬细胞易于摄入脂质转变为泡沫细胞有关,对动脉粥样硬化早期病变的形成和发展可能具有重要作用。     

丁酸钠对50%总体表面积烫伤大鼠肺血管内皮糖萼层保护作用和机制研究

目的研究丁酸钠对严重烫伤大鼠肺血管内皮糖萼层的保护作用及可能机制。 方法将144只成年雄性SD大鼠按照随机数字表法分成假伤＋盐水组(n＝24),假伤＋丁酸钠组(n＝24),烫伤＋盐水组(n＝48),烫伤＋丁酸钠组(n＝48)。制作50%总体表面积Ⅲ度烫伤模型：烫伤＋盐水组和烫伤＋丁酸钠组大鼠麻醉、备皮后置于80 ℃水浴锅中(背部15 s,腹部8 s,双下肢15 s),假伤＋盐水组和假伤＋丁酸钠组大鼠浸入37 ℃水相同时间。假伤＋丁酸钠组和烫伤＋丁酸钠组立即皮下注射丁酸钠(300 mg/kg);假伤＋盐水组和烫伤＋盐水组立即皮下注射0.5 mL 0.9%氯化钠溶液。于伤后3、6 h分别处死动物并取材,测定肺泡灌洗液蛋白(BALF)浓度,肺湿干重比;采用蛋白质印迹法和酶联免疫法检测肺组织多配体蛋白聚糖-1(SDC-1)、基质金属蛋白酶9(MMP-9)和血管内皮生长因子(VEGF)的蛋白表达和含量率的变化。数据比较采用单因素方差分析和Newman-Kueuls法。 结果(1)伤后3、6 h,烫伤＋盐水组BALF蛋白浓度分别为(0.657 5±0.045 5)、(0.684 1±0.076 0) mg/mL,高于假伤＋盐水组[(0.476 6±0.065 8) mg/mL],差异均有统计学意义(q＝7.188、8.243,P值均小于0.05);伤后3、6 h,烫伤＋盐水组肺湿干重比分别为4.545 1±0.444 4,4.795 1±0.606 6,均高于假伤＋盐水组(2.636 0±0.157 5),差异均有统计学意义(q＝10.950、12.380,P值均小于0.05)。伤后3、6 h,烫伤＋丁酸钠组BALF蛋白浓度分别为(0.541 0±0.071 )、(0.538 1±0.063 6) mg/mL,均低于烫伤＋盐水组[(0.657 5±0.045 5)、(0.684 1±0.076 0) mg/mL],差异均有统计学意义(q＝4.610、5.799,P值均小于0.05);且伤后3、6 h,烫伤＋丁酸钠组肺湿干重比值3.626 6±0.446 1、3.477 9±0.510 7,均低于烫伤＋盐水组,差异均有统计学意义(q＝5.269、7.555,P值均小于0.05)。(2)蛋白质印迹法检测结果显示,伤后3、6 h,烫伤＋盐水组肺组织SDC-1表达水平分别为0.376 1±0.075 7、0.329 8±0.074 9,假伤＋盐水组肺组织SDC-1表达水平均为1.000 0±0,2组比较差异均有统计学意义(q＝13.280、14.260,P值均小于0.05)。伤后3、6 h,烫伤＋丁酸钠组肺组织SDC-1表达水平分别为0.760 5±0.207 1、0.678 3±0.117 9,均高于烫伤＋盐水组,差异均有统计学意义(q＝8.180、7.417,P值均小于0.05)。伤后3、6 h,烫伤＋盐水组肺组织MMP-9、VEGF表达水平分别为(MMP-9：2.683 4±0.318 8、2.655 6±0.448 9;VEGF：3.806 3±0.703 8、2.850 0±0.396 3),假伤＋盐水组MMP-9、VEGF表达水平均为1.000 0±0,烫伤＋盐水组均低于假伤＋盐水组,差异均有统计学意义[(MMP-9: q＝9.356、9.202),(VEGF: q＝12.700、8.375); P值均小于0.05 ]。伤后3、6 h,烫伤＋丁酸钠组肺组织MMP-9、VEGF表达水平分别为(MMP-9：0.995 2±0.378 5、1.527 1±0.342 8;VEGF：1.574 6±0.216 0、1.721 5±0.341 8),均低于烫伤＋盐水组,差异均有统计学意义[(MMP-9: q＝9.383、10.100),(VEGF: q＝6.272、5.108); P值均小于0.05]。(3)酶联免疫法检测结果显示,伤后3、6 h,烫伤＋盐水组与假伤＋盐水组比较,肺组织MMP-9、VEGF蛋白含量均显著增高,差异均有统计学意义[(MMP-9: q＝8.850、8.436), (VEGF：q＝9.090、9.186); P值均小于0.05];SDC-1蛋白含量显著降低,差异均有统计学意义(q＝8.296、8.331,P值均小于0.05)。伤后3、6 h,烫伤＋丁酸钠组肺组织MMP-9、VEGF蛋白含量均低于烫伤＋盐水组,差异均有统计学意义[(MMP-9: q＝6.579、6.939),(VEGF：q＝7.853、7.768);P值均小于0.05];SDC-1蛋白含量高于烫伤＋盐水组(q＝6.265、4.456,P值均小于0.05)。 结论丁酸钠能减轻严重烫伤大鼠肺组织水肿,保护肺血管内皮糖萼层,其作用机制可能与抑制MMP-9和VEGF通路相关。     

乙酰肝素酶在子宫内膜癌组织中的表达及血管生成、浸润的关系

目的探讨乙酰肝素酶（Heparanase，Hpa）在子宫内膜癌组织中的表达及预后关系。方法采用S—P免疫组织化学法检测Hpa和CD34蛋白在子宫内膜癌组织和正常子宫内膜组织中的表达，并结合病理学分型、组织学分级、微血管密度（MVD）和临床分期探讨其意义。结果子宫内膜癌Hpa蛋白的表达显著高于正常子宫内膜（P〈0．05），子宫内膜癌组织中Hpa蛋白的表达与子宫内膜癌组织血管生成、病理分型、分期有关（P〈0．05）。结论Hpa蛋白在子宫内膜癌中呈高表达，并与子宫内膜癌血管生成、病理特征有关，检测其表达以对判断子宫内膜癌的生物学行为提供指标。     

内皮脂酶在动脉粥样硬化及冠心病中的研究进展

内皮脂酶(endothelial lipase,EL)是近年来发现的三酰甘油脂肪酶基因家族的新成员,它是HDL代谢的关键酶.EL通过降解HDL而在冠心病发病过程中起着重要作用.近年来的基础研究发现:EL参与了脂质代谢、内皮损伤、炎症反应这三个动脉粥样硬化(atherosclerosis,AS)形成的关键过程,因此EL可能是AS形成的枢纽及媒介.临床研究也表明EL可能是冠心病的重要危险因素.但目前EL与冠心病关系的研究多为基础研究,临床研究尚刚刚起步.     

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging.     

带糖萼层的大分子跨动脉壁传质模型研究

目的 通过研究复杂血管内的糖萼层、高血压等因素对大分子跨血管壁传输的影响,为进一步认识动脉粥样硬化的成因提供了理论依据。方法 考虑动脉壁的生理结构：内皮、内膜、内膜弹性层、中膜和糖萼层,建立了动脉壁中大分子跨壁传质的5层多孔介质模型。假设动脉为一段轴对称长直圆管,血浆为牛顿流体,用解析法得到稳态流动下的动脉壁内血浆渗流速度和大分子浓度分布。结果 糖萼层的厚度对血浆渗流速度的影响几乎可以忽略。糖萼层的厚度越大,对大分子传质的阻碍作用越明显。糖萼层的存在降低了高血压对大分子传质的影响。结论 糖萼层对大分子跨壁传质有很大的阻碍作用,即使在高血压情况下,内膜层大分子浓度的增幅也非常小。因此,糖萼层的存在能有效降低因高血压引起的大分子跨血管过度传输。     

粘着斑激酶在血管内皮细胞迁移中的作用

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase (PTK) that can localize indirectly to sites of clustering integrin family of heterodimeric receptors. As an important structure and signaling molecule in the adhesive complexes, which are large and stable referred as ‘focal adhesions‘ or relatively small and transient within filopodia and lamellipodia named ‘focal complexes‘, FAK is closely related with cell death, proliferation and migration. In this review, we discuss the function of FAK in the regulation of endothelial cell migration based on current data.     

Effects of vascular endothelial growth factor released from cultured dermal substitute on proliferation of vascular endothelial cells in vitro

Allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts on a two-layered spongy matrix of hyaluronic acid and atelocollagen. CDS can be cryopreserved and transported to other hospitals in a frozen state. The present study was designed to analyze the amounts of vascular endothelial growth factor (VEGF) released from fibroblasts in fresh and cryopreserved CDS and to investigate the effects of this VEGF on proliferation of vascular endothelial cells in vitro. The culture medium used in preparing CDS (fresh CDS culture medium sample) was collected and stored at –30°C for the quantitative analysis of VEGF. After thawing cryopreserved CDS, it was recultured in a culture medium for 1 week. The culture medium used was collected and stored at –30°C for quantitative analysis of VEGF. The amounts of VEGF released from the fresh and cryopreserved CDS into the culture medium were about 610pg/ml and 640pg/ml, respectively. This finding suggests that the cryopreserved CDS retains its ability to release VEGF. Immunohistological analysis indicated that some of the VEGF adhered to the matrix. Human vascular endothelial cells were cultured in medium mixed with the fresh or cryopreserved CDS culture medium sample. Proliferation of vascular endothelial cells was enhanced by increasing the concentration of both CDS culture medium samples. When antihuman VEGF antibody was added to the culture medium, the proliferative activity of vascular endothelial cells was reduced. These findings confirm that VEGF released from CDS promotes proliferation of vascular endothelial cells.     

Impact of inflammation on vascular disease in hypertension

Low grade inflammation exerts a crucial pathogenic role in hypertension and cardiovascular disease. A large body of evidence indicates that innate and adaptive immune systems, and in particular T cells, are involved. A balance between T-effector lymphocytes and T_reg lymphocytes represents a crucial regulatory mechanism that, when altered, favours blood pressure elevation and organ damage development. Of note, T_reg lymphocytes exert important anti-inflammatory properties, whose activities guarantees vascular homeostasis and protects the vessel wall from the development of atherosclerosis. In humans, most of evidence ascertaining essential hypertension as a condition of chronic low-grade inflammatory status revealed a strict and independent association between CRP, TNF-α, IL-6 or adhesion molecules and vascular changes in essential hypertensive patients. Evidence of involvement of the immune system in vasculature from patients with hypertension or cardiovascular disease starts to appear in literature.     

血管内皮生长因子的免疫学测定法

目的：检测肿瘤细胞条件培养液中ＶＥＧＦ的表达量。方法：在表达及分离纯化ＶＥＧＦ的基础上,成功地制备了ＶＥＧＦ抗体,以夹心法测定ＶＥＧＦ,ＶＥＧＦ测定范围为０．０２～２００．００ｎｇ／ｍｌ,灵敏度可达０．０２ｎｇ／ｍｌ,批内及批间变异均小于１０％,回收率平均为１０２．４％。其中人胃癌细胞ＭＧＣ８０３、ＢＧＣ８２３、乳癌ＮＭＣＦ－７及肝癌ＢＥＬ－７４０２分泌上清中ＶＥＧＦ的含量分别为６．５０、０．４５     

血管内皮生长因子及其受体在子宫内膜异位症中的表达和意义

目的:研究血管内皮生长因子(Vascular endothelial growth factor,VEGF)及其受体(Vascular endothelial growth factor receptor1,VEGFR1)在子宫内膜异位症(内异症)患者子宫在位内膜、异位内膜及正常对照组内膜组织中的表达,探讨其在子宫内膜异位症中的作用机制.方法:采用免疫组织化学及Western blot方法检测34例异位症患者在位内膜、异位内膜(内异症组)及34例正常内膜(对照组)组织中VEGF及其受体VEGFR1蛋白的定位及表达.结果:异症组在位及异位子宫内膜组织腺上皮细胞及间质细胞中均有VEGF及VEGFR1蛋白表达,且均高于同期对照组内膜,差异有统计学意义;对照组分泌期内膜VEGF及VEGFR1蛋白表达高于增生期,呈现周期性变化,而内异症组在位及异位内膜VEGF及VEGFR1蛋白表达失去周期性变化,分泌期与增生期均高表达,差异无统计学意义.Western blot检测结果与免疫组化结果一致.结论:内异症患者在位及异位内膜组织中VEGF、VEGFR1蛋白高表达可能与内异症的发生发展有关.