1-磷酸鞘氨醇对血小板活化因子所致大鼠肠系膜微血管通透性增高的影响  

Effect of sphingosine 1-phosphate on increase in microvessel permeability induced by platelet activating factor

作　　者：臧婵媛[1] 康毅[1] 温克[1] 娄建石[1] 

机构地区：[1]天津医科大学药理学教研室,天津300070

出　　处：《中国病理生理杂志》2010年第4期681-685,共5页Chinese Journal of Pathophysiology

基　　金：高等学校博士学科点专项科研基金资助项目(No.20070062009);天津医科大学科学基金资助项目(No.2009ky02)

摘　　要：目的:探讨1-磷酸鞘氨醇(S1P)对血小板活化因子(PAF)引起的大鼠肠系膜微血管通透性增高的影响。方法:本研究拟采用大鼠在体肠系膜微血管灌注的方法,通过测定微静脉的静水传导性(Lp),观察S1P对外源性PAF引起的微血管通透性增高的影响;并利用激光共聚焦显微镜技术,观察S1P对PAF引起的微血管荧光强度变化以及血管内皮细胞钙粘蛋白(VE-cadherin)变化的影响。结果:给予10nmol/LPAF作用后,大鼠肠系膜微血管Lp值明显增高,而经1μmol/L S1P预处理后,再给予PAF并未引起Lp的明显变化;PAF作用微血管后可见微血管内皮细胞间隙打开,微血管荧光强度明显增加,大量红色荧光微球(FMs)分布于内皮细胞间隙之中,S1P预处理后并未见内皮细胞间隙打开及FMs的明显积聚,微血管荧光强度与正常对照值比较无显著差异。结论:PAF可增加微血管的通透性,改变内皮细胞VE-cadherin正常结构,导致粘附连接断裂,细胞间隙形成,血管通透性增加可能与此结构变化有关。S1P能改善PAF引起的血管通透性增高,其作用与加强内皮细胞间粘附连接,抑制细胞间隙打开有关。AIM：To study the effect of sphingosine 1-phosphate （S1P） on the increase in microvessel permeability induced by platelet activating factor （PAF）. METHODS： The microvessel permeability was assessed by measuring hydraulic conductivity （Lp）. To observe the effect of S1P and PAF on vascular endothelial-cadherin （VE-Cadherin）,the microvessels were stained with immunofluorescence and examined by laser confocal microscopy. RESULTS： After giving PAF at concentration of 10 nmol/L,the Lp value of rat mesentery microvessel was significantly increased. However,after pretreatment with S1P,PAF did not give rise to a further significant change. The effect of PAF on microvascular endothelial cells could be seen： the formation of endothelial gap was induced,the microvascular fluorescence intensity significantly increased,a large number of fluorescent microspheres （FMs） distributed in the space among the endothelial cells. However,after pretreated with S1P,no obvious gap opening and the FMs accumulation were observed. Compared to normal control,no significant difference of the microvascular fluorescence intensity was found. CONCLUSION： PAF changes the structure of VE-Cadherin,leading to detachment of adherent junction,formation of intercellular gaps,which contributes to the increase in the permeability. S1P improves the increase in the microvessel permeability caused by PAF,which might be mediated by strengthening adherent junction and inhibiting the formation of endothelial gaps.

关 键 词：微血管通透性 1-磷酸鞘氨醇 血小板活化因子 静水传导性 血管内皮钙粘蛋白 

分 类 号：R563[医药卫生—呼吸系统]