前列腺素E2(PGE2)在烧伤后大鼠血管内皮细胞分泌的机制研究

摘要

目的 明确外周烧伤是否可引起中枢神经系统血管内皮细胞前列腺素E2增加及其发生机制.方法 试验大鼠(SD大鼠)接受约25%的全层(Ⅲ度)烧伤,并进行相关治疗,在36小时后,对大鼠脑脊液进行采样,测量其中的前列腺素E2(PGE2)含量,同时对大鼠脑和脊椎组织进行免疫组化研究,对其中与前列腺素合成有关的2种重要酶,环氧化酶2(COX-2)和微粒体前列腺E2合成酶(mPGES)进行分析.结果 在烧伤后的大鼠脑脊液中,前列腺素E2的含量明显增加,但可以被环氧化酶2的选择性抑制剂NS398所抑制.在烧伤后,对大鼠中枢神经系统血管内皮细胞的免疫组化研究可以发现COX-2和mPGES.双重免疫荧光法发现这2种酶主要集中在内皮细胞的核周.结论 外周的烧伤主要通过诱导中枢神经内皮细胞产生COX-2和mPGES.这些酶可以提高脑脊液中的前列腺素E2浓度,从而激活中枢神经系统前列腺素E2的受体,产生烧伤后的全身症状.适当的应用COX-2抑制剂,使烧伤患者的PGE2水平处在对机体有利的合适范围内,不仅可以减少患者的临床的不适症状,以减轻烧伤早期损害和第二次打击时机体失控的炎症反应,而且可以减少患者感染的发生率.%Objective Methods To examine whether peripheral burn injury in rats elevates prostaglandin EZ in the central nervous system and to determine where in the central nervous system enzymes responBible for prostaglandin E2 synthesis arc expressed. Subjects: Spraguc-Dawley rats. Interventions; Rats received either approximately 25% fullthickness burn injury or sham treatment. At 36 hrs after the injury, the cerebrospinal fluid was sampled to measure prostaglandin E2,and the brain and the spinal cord were sampled for immunohistochemical detection of cyclooxygcnasc-2 and microsomal-typc prostaglandin E2 synthasc,enzymes that arc responsible for prostaglandin E2 production. Measurements and Main. Results The prostaglandin E2 concentration in the ccrcbrospinal fluid was significantly elevated in the injured rats,and this elevation was suppressed by a cyclo-oxygcnasc-2-spccific inhibitor, NS398. Only in the injured rats,cyclooxygcnasc-2 and microsomal-typc prostaglandin E synthasc proteins were detected in vascular cndothelial cells throughout the central nervous system with no regional difference. A double-immunofluorcsccncc study revealed that cyclooxygcnasc-2 and microsomal-typc prostaglandin E synthasc were coexpresscd in the pcrinuclcar region of the cndothclial cells. Conclusion These results indicate that peripheral burn injury induces cyclooxygcnasc-2 and microsomal-typc prostaglandin E synthasc in cndothclial cells of the central nervous system. These enzymes likely elevate the ccrcbrospinal fluid concentration of prostaglandin E2,a prostanoid that,in turn,activates prostaglandin E2 receptors on the central nervous system neurons involved in the general symptoms following burn injury.