前列腺素E_2及其受体EP3A与创伤性脑水肿的关系

Experimental Study of Correlation between Prostaglandin E 2 with Its Receptor EP3A Subtype and Traumatic Brain Edema

目的：研究前列腺素Ｅ２（ＰＧＥ２）及其受体ＥＰ３Ａ与创伤性脑水肿的关系．方法：运用形态学、放射免疫及分子生物学等方法，对模型脑外伤大鼠伤区及创伤对侧相应区域脑含水量、血脑屏障（ＢＢＢ）通透性、ＰＧＥ２含量、ＥＰ３ＡｍＲ－ＮＡ表达，以及消炎痛对其影响进行动态定量检测．结果：（１）伤后２小时，伤区脑组织ＰＧＥ２及含水量显著增高（Ｐ＜０．０５），ＢＢＢ严重破坏．这些变化于伤后２４小时达高峰，伤后４天均显著下降．消炎痛预处理动物可显著减轻上述变化．（２）伤后２小时，伤区脑组织ＥＰ３ＡｍＲＮＡ密度显著下降（Ｐ＜０．０５），伤后２４小时降到最低，伤后４天又开始回升．在创伤对侧或远离伤区，ＥＰ３ＡｍＲＮＡ密度则显著高于伤区，接近正常水平．应用消炎痛，在伤区病变好转的同时，也可见ＥＰ３ＡｍＲＮＡ密度的增加．结论：（１）ＰＧＥ２与脑含水量及血脑屏障通透性呈显著正相关，参与了创伤性脑水肿的发生发展．（２）伤后脑组织ＥＰ３ＡｍＲＮＡ表达似与脑组织伤后自我保护机制有关．（３）消炎痛可以减轻大鼠伤后脑组织的继发性损害．

Aim: To study the correlation between prostaglandin E 2 (PGE 2) with its receptor EP3A subtype and traumatic brain edema. Methods: A quantative measurement of water content, permeability of blood brain barrier (BBB), PGE 2 and EP3A mRNA as well as the effect of indomethacin, both on the damage site and the opposite site were carried out by use of morphology, radioimmunoassay and dot hybridization. Results: 1. Two hours after trauma, the production of prostaglandin E 2 and cerebral water content increased significantly ( P <0.05), while the integrity of BBB was disrupted severely at the injury site, and these changes reached peak at 24 hours and decreased significantly ( P <0.05) 4 days later. Pretreatment with indomethacin could alleviate the changes markedly. 2. The density of EP3A mRNA at the site of contusion decreased significantly 2 hours after trauma ( P <0.05), became lowest at 24 hours, and began to recover 4 days later. In the controlateral or distant site from the impact, the density of EP3A mRNA increased significantly versus the normal ( P <0.05). By use of indomethacin, the incresase of EP3A could be seen at the same time as the brain tissue at injured region came to heal. Conclusion: 1. PGE 2 involves in the generation and development of vasogenic brain edema after trauma. 2. Expression of EP3A mRNA after brain injury seems to be involved in the protection of brain tissue. 3. Indomethacin can alleviate the secondary brain damage.