脑损伤后早期前列腺素的变化及消炎痛的干预作用

背景颅脑损伤诱发的花生四烯酸代谢瀑布过程中产生的前列腺素类和氧自由基的增加是其重要的一方面,消炎痛能强烈抑制环氧化酶活性,减少前列腺素类合成,并可能减少氧自由基的增加,从而可能具有减轻脑损伤作用.目的观察脑损伤后早期前列腺素的变化及消炎痛对其的干预作用,探讨其作用机制.设计以实验动物为研究对象,随机对照实验研究.单位一所大学医院的神经外科和一所大学医院的脑外科.材料实验于2000-03/09在东南大学医学院神经外科实验室完成.将36只杂种猫,随机分为正常对照组,脑损伤组和消炎痛干预组3组,每组12只.干预脑创伤按分级机械脑损伤实验动物模型制作,取中度脑损伤水平进行研究.伤后6h测定脑静脉血中前列腺环素(PGI2)和血栓素(TXA2)的最终分解产物6-酮-前列腺素F1a(6-keto-PGF1α)和血栓烷素B2(TXB2)、脑组织总超氧化物歧化酶(SOD)及脑含水量.主要观察指标6-keto-PGF1α,TXB2,SOD含量和脑含水量测定.结果猫脑损伤后早期脑静脉中6-keto-PGF1α和TXB2均明显增加[由(0.057±0.010)g/L增至(0.264±0.126)g/L,由(0.060±0.012)g/L增至(0.134±0.048)g/L,6-keto-PGF1α增幅大于TXB2,TXB2/6-keto-PGF1α比值下降(由1.052±0.145降为0.545±0.184),脑含水量增加[由(77.39±0.36)%增至(78.06±0.41%)],同时脑组织总SOD明显降低[由(94.869±5.418)μkat/g降至(54.368±3.417)μkat/g](P＜0.01);消炎痛干预组与脑损伤组比较,6-keto-PGF1α和TXB2明显降低,与正常对照组接近,而总SOD则有增加[(54.368±3.417)μkat/g增至(81.433±7.268)μkat/g](P＜0.01),脑含水量略降低,但无统计学意义(P＞0.1).结论猫脑损伤后早期PGI2和TXA2增加,并伴随自由基产生,由此加重脑损害.消炎痛通过调节脑损伤后PGT2/TXA2失衡,减少自由基产生,有助于减轻脑创伤后继发性脑损害.

Changes of prostaglandin in early brain injury and therapeutic effect of indomethacin

BACKGROUND: Traumatic brain injury generates a cascade of arachidonic acid metabolic events that mainly presented by the increment of prostaglandin and oxygen free radicals. Indomethacin can potently inhibit the activity of cyclooxygenase, decrease the synthesis of prostaglandins, and may decrease the production of oxygen free radical, and thus may attenuate the pathological changes of brain injury.OBJECTIVE: To observe the changes of prostaglandin in early brain injury and after indomethacin intervention, so as to explore the pharmacological mechanism of indomethacin.DESIGN: A randomized and controlled trial based on experimental animals.SETTING: Department of neurosurgery and department of cerebral surgery in a university hospital.MATERIALS: This study was carried out at the Laboratory of Neurosurgery Department, Medical College of Southeast University between March and September 2000. Thirty-six hybrid cats were randomly divided into normal control group, brain injury group and indometbacin intervention group, with 12 cats in each group.INTERVENTIONS: Brain injury was simulated according to previously reported grading mechanical traumatic animal model establishment; cats with medium brain injury were enrolled in this study. The ultimate concentrations of prostacyclin (PGI2) and thromboxane A (TXA2) to 6-keto-prostaglandin F 1 alpha(6-keto-PGF1α) and thromboxane B2(TXB2) in brain vein blood, as well as total brain superoxide dismutase(SOD) and cerebral water content were measured 6 hours after trauma.MAIN OUTCOME MEASURES: 6-keto-PGF1α, TXB2, SOD, and cerebral water content.RESULTS: Both 6-keto-PGF1α and TXB2 in brain vein blood remarkably increased in early brain injury[from(0.057±0.010) g/L to (0.264±0. 126) g/L, from(0. 060 ±0. 012) g/L to(0. 134 ±0. 048) g/L respectively], with the increment of the former higher than the latter, the ratio of TXB2/6-keto-PGF1α decreased from 1. 052 ±0. 145 to 0. 545 ±0. 184, and cerebral water content increased from(77.39 ± 0. 36)% to (78.06±0.41)% ; meanwhile, total brain SOD significantly decreased from (94. 869 ± 5. 418) μkat/g to(54. 368 ± 3. 417) μ kat/g( P ＜ 0.01) . In contrast to brain injury group, the concentrations of 6-keto-PGF1α and TXB2 in indomethacin intervention group significantly decreased, which were similar to those of control group, but the total SOD significantly increased from (54. 368 ±3. 417) pkat/g to (81. 433 ±7. 268) μkat/g (P ＜0. 01), and water content lightly decreased without statistical significance( P ＞ 0. 1 ).CONCLUSION: PGI2 and TXA2 increase in early brain injury in experimental cat model, accompanied by free radical synthesis, resulting in the exacerbation of brain injury. Indomethacin may be helpful to relieve posttraumatic secondary brain injury by regulating the imbalance of PGT2 / TXA2 and decreasing the production of free radical.