TNFα、ET及NO与妊高征胎盘和脐血管内皮细胞损伤的关系

目的：探讨肿瘤坏死因子α（TNFα）、内皮素（ET）及一氧化氮（NO）在妊娠高血压综合征（简称妊高征）发病机制中的意义。方法：17例正常孕妇和41例妊高征孕妇在产前产后分别测定血TNFα、ET及NO水平；用电镜观察胎盘和脐血管内皮细胞超微结构。结果：（1）妊高征患者产前血TNFα和ET水平均明显升高，NO水平下降，随病情加重而更明显；产后72TNFα和ET水平下降，NO水平增高。(2)妊高征患者胎盘和脐血管内皮细胞均有损伤性表现，且与产前血TNFα变化相一致。结论：妊高征患者胎盘和脐血管内皮细胞的损伤和功能性变化与血TNFα水平增高有关，TNFα可能作为血管内皮损伤的一种免疫因子引发妊高征。     

严重烧伤后中性粒细胞对血管内皮细胞形态与功能的影响及参麦注射液对其作用的实验研究

目的 了解严重烧伤后中性粒细胞(PMN)对血管内皮细胞形态与功能的影响及参麦注射液对内皮细胞的保护作用.方法 从健康体检者和烧伤患者(伤后6、24、48 h)静脉血中分离出PMN,与血管内皮细胞株ECV304体外共培养,采用噻唑蓝法检测ECV304细胞活力.放射免疫法检测培养上清液中内皮素1、一氧化氮(NO)的含量,并计算两者的比值(内皮素1/NO).另取伤后24 h血液标本与ECV304共培养,分别加入等渗盐水及0.5、2.0、8.0 g/L参麦注射液各100 μL,观察参麦注射液对上述指标及ECV304形态的影响.结果 与健康体检者比较,在伤后6 h的PMN刺激下ECV304活力明显下降、内皮素1含量明显上升(P＜0.01),伤后24 h的PMN刺激时尤为显著;而伤后6 h在PMN刺激下NO含量明显上升达峰值[(48.9±2.6)μmol/L,P＜0.01],伤后24,48 hPMN刺激ECV304的NO含量与健康体检者比较,无明显差异(P＞0.05);内皮素1/NO的变化趋势同内皮素1.加入不同浓度参麦注射液共培养后,可使内皮细胞活力明显上升、内皮素1含量明显下降、NO含量明显升高,其中中浓度参麦注射液可使体系中内皮细胞形态近似正常.结论 严重烧伤后PMN对血管内皮细胞形态、细胞活力、内皮素1/NO均有不同程度的影响,且以伤后24 h的PMN刺激最明显;参麦注射液可以改善上述情况,对严重烧伤后血管内皮细胞损伤具有保护作用.     

激素性骨坏死血管变化的实验研究

目的观察激素性骨坏死动物血管功能障碍,血管损伤,血流粘滞和血管再生障碍变化的规律和过程。方法选用中国白兔随机分2组。A组：马血清加用甲基强的松龙组;B组：单用甲基强的松龙组。A、B组分别于用药前及最后一次用激素后3、7、21d测定血浆内皮素（ET）、细胞间粘附分子-1（ICAM-1）和血栓调节蛋白（TM）。A组动物于首次注射血清1周,首次应用激素后1、3、5、7周;B组动物于首次注射激素后1、3、5、7周分批处死取双侧股骨头。常规HE染色和VEGF免疫组化染色。结果血清加激素组的变化较单纯应用激素组有更强的变化;血清加激素组动物ICAM-1和TM在应用激素后3周时已开始回复,而ET未见回复;2组动物的VEGF表达都表现为降低后逐渐回复的过程。结论应用激素后,股骨头普遍存在前坏死状态,这种情况具有一定的可恢复性,但恢复结果可能受多种因素影响,因而应对这类情况进行长期的观察。     

孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用

目的探讨孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用价值。方法选择30例子痫前期孕妇为子痫前期组(其中轻度18例,重度12例),另选择30例正常孕妇作为对照组,两组孕妇分别于孕20周、孕晚期(子痫前期组孕33周+3、对照组孕34周+3)、分娩后1、3、6 h取外周血,采用荧光定量PCR检测外周血中Y染色体上的性别决定基因(SRY基因)胎儿DNA水平(B超确定两组孕妇所妊娠的胎儿均为男性);放射免疫法检测两组孕妇孕晚期内皮素水平。结果(1)子痫前期组孕20周时的胎儿DNA水平为(316±61)copy/m l,其中轻度、重度患者分别为(266±79)、(396±91)copy/m l;对照组孕妇为(165±43)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(2)子痫前期组孕晚期胎儿DNA水平为(970±413)copy/m l,其中轻度、重度患者分别为(758±357)、(1285±573)copy/m l,对照组孕妇为(319±99)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(3)子痫前期组产后1、3、6 h胎儿DNA水平分别为(139±45)、(76±31)、(44±13)copy/m l,其中轻度患者分别为(102±42)、(57±25)、(36±12)copy/m l,重度患者分别为(209±51)、(97±40)、(52±17)copy/m l;对照组分别为(33±13)、(9±5)、0 copy/m l。子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(4)子痫前期组内皮素水平为(80±18)ng/L,其中轻度患者为(74±14)ng/L,重度患者为(89±32)ng/L;对照组为(50±11)ng/L,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(5)子痫前期组胎儿DNA水平与内皮素水平呈正相关关系(r=0.748,P<0.01)。结论孕妇外周血胎儿DNA水平变化可以作为预测和诊断子痫前期发病与疾病程度的一个指标。     

术前肌注咪唑安定对听觉诱发电位指数和血浆内皮素的影响

目的　比较和评价麻醉手术前使用咪唑安定或苯巴比妥钠对患者焦虑、顺行性遗忘、听觉诱发电位指数和血浆内皮素的影响。方法　 4 0例年龄 2 0～ 6 0岁、ASAⅠ～Ⅱ级的择期手术患者 ,随机分为两组。Ⅰ组麻醉前 30min肌肉注射苯巴比妥钠 0 1g +阿托品 0 5mg(n =2 0 ) ;Ⅱ组于麻醉前 30min肌肉注射咪唑安定 0 0 6mg/kg(41～ 6 0岁 )和 0 0 8mg/kg(2 0～ 4 0岁 ) +阿托品 0 5mg(n=2 0 )。分别于用药前后测定患者收缩压 (SBP)、舒张压 (DBP)、心率 (HR)、指脉搏血氧饱和度(SpO2 )、呼吸频率 (RR)、焦虑视觉模拟评分 (AVAT)、听觉诱发电位指数 (AEPI)、顺行性遗忘程度和血浆内皮素 (ET 1)浓度变化。结果　两组患者在用药前后SBP、DBP、HR、SpO2 和RR无明显变化(P >0 0 5 ) ;Ⅰ组在用药前后AVAT、AEPI和ET 1浓度变化无差异 (P >0 0 5 ) ,顺行性遗忘率 2 0 % ;Ⅱ组用药后 30minAVAT、AEPI和ET 1浓度均低于用药前 (P <0 0 5 ) ,顺行性遗忘率为 75 %显著高于Ⅰ组 (P <0 0 1)。结论　与苯巴比妥钠相比 ,咪唑安定可有效减轻患者麻醉手术前焦虑情绪 ,获得更好的顺行性遗忘和镇静效果 ,且能减轻麻醉手术前应激反应     

Bosentan, an endothelin receptor antagonist, reduces leucocyte adhesion and inflammation in a murine model of inflammatory bowel disease

Background and aims Endothelins, a group of polyfunctional cytokines, induce the adhesion of circulating leucocytes to venous endothelium, an initial step in the pathogenesis of a cellular infiltrate in inflammatory bowel disease (IBD). The effect of bosentan, a non-selective endothelin receptor antagonist, on leucocyte adhesion and inflammation in a murine model of IBD was studied.Materials and Methods Thirty BALB/c mice were divided into three groups of 10 animals: untreated controls, chronic colitis [dextran sodium sulphate (DSS), 3% w/v for 30 days], and treatment with bosentan (30 mg/kg i.p. daily on days 26–30). On day 30, adherent and rolling leucocytes and the average rolling velocity were assessed by intravital microscopy. Clinical and histological activity of inflammation were assessed by the disease activity index and modified Dieleman score, respectively.Statistics Kruskal–Wallis test was used, followed by Dunn's method. A value of p<0.05 was considered significant.Results Compared to healthy controls, mice treated with DSS showed pronounced clinical and histological inflammation, and a higher number of rolling and adhering leucocytes in colonic submucosal venules. Therapy with bosentan significantly reduced clinical and histological inflammation. Adherent leucocyte levels were markedly lower (1.2±0.3 vs 23.7±2.8 adherent cells per 0.01 mm², p<0.05). The number of rolling leucocytes was lower but not significantly different. However, rolling velocity was significantly higher (91.5±14.0 vs 19.0±1.6 μm/s, p<0.05).Conclusions Bosentan reduces the adhesion of leucocytes in colonic submucosal venules and reduces inflammation in this mouse model of IBD. By inhibiting leucocyte adhesion, a crucial step in the recruitment of leucocytes to the inflamed tissue, bosentan is a potent therapeutic drug in this animal model. Further studies are necessary to investigate the role of bosentan as a novel drug in human IBD.C. Anthoni and R.B. Mennigen contributed equally to this work     

Systemic and renal effects of an ETA receptor subtype-specific antagonist in healthy subjects

1. Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ET_A receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1.
2. The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way cross-over design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg⁻¹ min⁻¹ for 120 min) or placebo and BQ-123 (15 μg min⁻¹ for 60 min and subsequently 60 μg min⁻¹ for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively.
3. BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (−24%, P<0.001) and GFR (−12%, P=0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020).
4. BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ET_A receptor subtype.

     

内皮素A受体拮抗剂BQ610对猫急性心肌缺血保护作用的超微结构观察

目的 观察内皮素Ａ受体拮抗剂ＢＱ６１０对急性缺血心肌超微结构的影响,以探讨内源性内皮素是否参与急性心肌缺血的病理过程。方法 结扎１２只猫左冠状动脉前降支（ＬＡＤ）造成急性心肌缺血,立即向已结扎的ＬＡＤ内直接注射ＢＱ６１０或注射生理盐水作对照,观察ＬＡＤ结扎后３０分钟缺血区及非缺血区心肌超微结构。结果 急性缺血区心肌出现肌细胞肿胀、肌原纤维排列紊乱及灶性溶解、线粒体肿胀及内皮细胞肿用 结构损伤,ＢＱ     

Endothelin-1 immunoreactivity in plasma is elevated in HIV-1 infected patients with retinal microangiopathic syndrome

Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving blood vessels. HIV-1 related retinal microangiopathic syndrome is a frequent finding in patients with AIDS or AIDS-related complex, presenting predominantly with retinal cotton-wool spots. We investigated 55 HIV-1 infected patients by ophthalmoscopy and for endothelin-I immunoreactivity in plasma and an additional 76 HIV-1 infected patients only for endothelin-1 levels. For reference values 13 age-matched healthy subjects were studied. In 18 of 55 patients (33%) investigated ophthalmoscopically we found evidence of microangiopathic syndrome. Overall, the mean endothelin-1 immunoreactivity in plasma of HIV-1 infected patients was significantly elevated as compared to controls (4.28 ± 3.62 versus 2.72 ± 0.67 fmol/ml, P < 0.0001). HIV-1 infected patients with retinal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreactivity (4.59 ± 1.38 fmol/ ml) compared to HIV-1 infected patients without microangiopathic syndrome (3.18 ± 1.64 fmol/ml, P = 0.003). Correlation analysis revealed that endothelin-1 immunoreactivity in plasma had no significant association with disease progression, CD4 cell count, ₂-mi-croglobulin, neopterin, or age. Endothelin-1 immunoreactivity in plasma was correlated exclusively with retinal microangiopathic syndrome in one or both eyes (r = 0.45, P = 0.0006) and with the number of cotton-wool spots (r = 0.50, P = 0.0001). In conlusion, HIV-1 related retinal microangiopathic syndrome is associated with elevated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may be involved in the pathogenesis of HIV-1 related vascular disease.Abbreviations AIDS aquired immunodeficiency syndrome - ET-1 endothelin-1 - HIV human immunodeficiency virus - IR immunoreactivity - WR Walter Reed classification Correspondence to: B. Rolinski     

胰腺癌患者血浆中内皮素水平变化及其意义的研究

目的　检测胰腺癌患者围手术期血浆中内皮素（ｅｎｄｏｔｈｅｌｉｎ , Ｅ Ｔ） 水平,探讨内皮素与胰腺癌的关系及其临床意义。 方法　 应用放射免疫分析法对胰腺癌３４ 例（ 胰头癌２７ 例,胰体尾癌７ 例）患者血浆中 Ｅ Ｔ 水平进行测定,并对其行姑息性手术及根治性手术前后 Ｅ Ｔ 水平的变化进行观察。结果　本组胰头癌患者术前 Ｅ Ｔ 水平〔（５８ ±７） ｎｇ／ Ｌ〕明显高于胰体尾癌组〔（５１ ±４） ｎｇ／ Ｌ, Ｐ＜ ００１〕及正常人组〔（５１ ±６） ｎｇ／ Ｌ, Ｐ＜ ００１〕,在减轻黄疸的手术后胰头癌组降至（５２ ±５） ｎｇ／ Ｌ,胰体尾组降至（５２ ±３） ｎｇ／ Ｌ 与正常水平相近。根治术后,胰头癌组 Ｅ Ｔ 水平为（５５ ±３） ｎｇ／ Ｌ,胰体尾癌组为（５３ ±３）ｎｇ／ Ｌ,均较姑息手术后有所升高,但差异均无显著意义（ Ｐ＞ ００５） 。 结论　 胰腺癌患者血浆中内皮素水平升高主要为合并梗阻性黄疸所致,胰腺癌虽可产生内皮素,但其可能仅是参与癌细胞间的调节作用。