1-磷酸鞘氨醇受体2抑制脂多糖诱导的急性肺损伤  

Sphingosine-1-phosphate receptor-2 attenuates lipopolysaccharide-induced acute lung injury

作　　者：李秀国[1] 延光海[1] 张永吉[1] 多久和阳 崔弘 

机构地区：[1]延边大学医学院,吉林延吉133002 [2]金泽大学大学院医学部循环医科学血管分子生理学,日本金泽920-8640

出　　处：《中国病理生理杂志》2015年第12期2239-2243,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81460001)

摘　　要：目的:探讨1-磷酸鞘氨醇受体2(S1P2R)对脂多糖(LPS)诱导的急性肺损伤(ALI)中的作用及机制。方法:野生小鼠和S1pr2-/-小鼠经气管滴注LPS,建立急性肺损伤动物模型。LPS注射24 h时观察肺组织的病理改变,测定支气管肺泡灌洗液(BALF)中的蛋白浓度、总细胞数、中性粒细胞的比值及TNF-α、IL-6细胞因子的表达。为了观察S1P2R在肺损伤中的作用机制,LPS注射10 min前野生小鼠和S1pr2-/-小鼠经尾静脉注射一氧化氮合酶抑制剂L-NAME,LPS注射12 h时,再观察肺的病理组织学变化以及BALF中的蛋白浓度,总细胞数及TNF-α、IL-6细胞因子表达的变化。结果:与野生小鼠比较,S1pr2-/-小鼠恶化LPS诱导的急性肺损伤,BALF中的蛋白浓度、总细胞数,中性粒细胞比值及炎症细胞因子表达显著增加。而L-NAME的预处理显著抑制在S1pr2-/-小鼠LPS诱导加重的急性肺损伤。结论:S1P2R通过抑制NO合成,维持血管屏障,从而抑制急性肺损伤。AIM： To investigate the effects and mechanisms of sphingosine-1-phosphate receptor-2（ S1P2R）on lipopolysaccharide（ LPS）-induced acute lung injury（ ALI）. METHODS： ALI model was induced by intratracheal administration of LPS in both wild-type mice and S1P2R-deficient mice. The pathological changes in the lung tissues were observed,and the protein concentration,total cell number,neutrophil ratio,TNF-α level and IL-6 level were determined in the bronchoalveolar lavage fluid（ BALF） 24 h after LPS injection. In order to investigate the mechanisms of S1P2 R in LPSinduced ALI,10 min before LPS injection,both wild-type mice and S1P2R-deficient mice were injected with nitric oxide synthase inhibitor by tail vein injection,the pathological changes of the lung tissues were observed,and the protein concentration and total cell number in BALF were determined 12 h after LPS injection. RESULTS： Compared with wild-type mice,S1P2R-deficient mice showed more severe LPS-induced ALI,and the protein concentration,neutrophils and inflammatory cytokines in BALF were significantly increased in S1P2R-deficient mice. Administration of nitric oxide synthase inhibitor Nω-L-nitro-arginine methyl ester protected S1P2R-deficient mice from aggravation of ALI. CONCLUSION： S1P2 R mediates the protection from LPS-induced ALI possibly through inhibiting nitric oxide synthase.

关 键 词：1-磷酸鞘氨醇受体2 急性肺损伤 一氧化氮 

分 类 号：R363.21[医药卫生—病理学]