脂多糖刺激人血管内皮细胞分泌内皮素和肾上腺髓质素及其机制研究  

Study on lipopolysaccharide-stimulated endothelin and adrenomedullin secretion from human vascular endothelial cells and its mechanism

作　　者：陈静炯[1] 龚永生[1] 徐雅琴[2] 许松[2] 柴三葆[2] 庞永正[2] 唐朝枢[2] 

机构地区：[1]温州医学院肺心病研究室,浙江温州325003 [2]北京医科大学第一医院心血管研究所,北京100034

出　　处：《中国病理生理杂志》2001年第5期403-406,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金!资助 (No .39730 2 2 0 )

摘　　要：目的 :研究脂多糖 (LPS)刺激人血管内皮细胞 (HVEC)分泌内皮素 - 1(ET - 1)与肾上腺髓质素 (Adm)的机制。方法 :在培养的HVEC上 ,用放射免疫法测定不同浓度LPS刺激HVEC分泌的ET - 1与Adm ,以及不同的细胞信号转导阻断剂对其分泌的影响。结果 :LPS呈时间和浓度依赖性地增加HVEC分泌ET - 1和Adm ,ET - 1/Adm比值与对照组比较无明显差异 (P >0 0 5 )。在LPS刺激基础上 ,细胞外信号调节激酶 (ERKs)抑制剂PD0 980 59和P38蛋白激酶抑制剂SB2 0 2 190 可明显降低LPS刺激HVEC分泌ET - 1(P <0 0 1) ,仅SB2 0 2 190 显著降低Adm的分泌 (P <0 0 5 ) ,其余PKC抑制剂H7,钙调素 (CaM)抑制剂W7,Ca2 + 阻断剂nicardipine,钙调神经磷酸酶 (CaN)抑制剂环孢霉素 (CsA)对LPS刺激HVEC分泌ET - 1和Adm均无明显影响 (P >0 0 5 )。结论 :LPS刺激HVEC分泌ET - 1可能与ERKs和P38两条途径有关 ,LPS刺激HVEC分泌Adm只与P38信号通路有关 ,两者均不取决于PKC、Ca2 + 、CaM、CaN依赖的信号通路。AIM: To study lipopolysaccharide (LPS)-stimulated secretion of endothelin-1 (ET-1) and adrenomedullin (Adm) from human vascular endothelial cells (HVEC) and its mechanism. METHODS: In cultured HVEC, LPS was used to stimulate ET-1 and Adm secretion from HVEC. The contents of ET-1 and Adm in medium were determined by radioimmunoassay. RESULTS: LPS stimulated secretion of ET-1 and Adm from HVEC in time-dependent and concentration-dependent manner. The ratio of secreted ET-1 to Adm was not changed compared with the control group. The increase of ET-1 could be inhibited by inhibitor of extracellular signal-regulated protein kinases (PD 098059 ) and inhibitor of P38 kinase (SB 202190 )( P< 0.01), while the increase of Adm could only be inhibited by SB 202190 ( P< 0.05), both had no response to inhibitor of protein kinase C (H 7), inhibitor of calmodulin (W 7), inhibitor of calcineurin (cyclosporin A) and inhibitor of Ca 2+ (nicardipine)( P> 0.05).CONCLUSION: ERKs and P38 signal pathways may play an important role in the secretion of ET-1 from LPS -stimulated HVEC, while only P38 kinase signal pathway is invovled in the secretion of Adm.

关 键 词：脂多糖类 内皮缩血管肽类 肾上腺髓质 信号传递 败血症 血管内皮细胞 

分 类 号：R515.3[医药卫生—内科学]