载脂蛋白E短肽COG1410对蛛网膜下腔出血后早期脑水肿的影响

Effect of apolipoprotein E mimetic peptide on cerebral edema in mice at early stage after subarachnoid hemorrhage

目的探讨载脂蛋白E短肽COG1410对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期脑损伤(early brain injury,EBI)中脑水肿、小鼠运动功能和水通道蛋白4(aquaproins-4,AQP-4)的影响。方法 108只C57BL/6J小鼠分成假手术对照组(sham)、生理盐水组(SAH+生理盐水)、治疗组(SAH+COG1410),采用血管内穿刺法建立SAH模型。观察小鼠运动功能变化,用干湿质量法测定脑含水量的变化,免疫组化法测定表达AQP-4阳性细胞数,酶联免疫吸附法(ELISA)测定AQP-4蛋白含量及实时定量PCR测定AQP-4 m RNA的变化。结果 SAH后生理盐水组和治疗组神经功能评分均明显高于假手术对照组(P<0.05),且生理盐水组和治疗组之间差异有统计学意义(P<0.05)。SAH后各时间点生理盐水组脑含水量、AQP4蛋白含量和AQP4 m RNA表达的变化与假手术对照组对比显著升高(P<0.05)。生理盐水组和治疗组脑含水量、AQP4蛋白含量和AQP4 m RNA表达均在SAH后1 d明显增加,2 d达到高峰,之后逐渐下降,2组间差异均有统计学意义(P<0.05)。结论载脂蛋白E短肽COG1410可能通过抑制AQP-4的过表达缓解EBI中的脑水肿。

Objective To investigate the effect of apolipoprotein E mimetic peptide COG1410 on the early cerebral edema, aquaproin4 （AQP-4） expression and movement function in mice with early brain injury （EBI） after subarachnoid hemorrhage （SAH）. Methods SAH model was established by endovascular perforation. A total of 108 male C57BL/6J mice were randomly divided into sham group, SAH ＋ saline group and SAH ＋ COG1410 group. The expression of AQP-4 in the brain of mice was measured by RT-PCR, immunohistochemistry and ELISA. The water content of the cerebral tissues was determined by the dry-wet weight method. Results After SAH, the nerve function scores of the SAH ＋ saline group and 5AH ＋ COG1410 group were significantly higher than those of the sham group （P 〈 0.05） , and there was statistically significant difference between the SAH ＋ saline group and the 5AH ＋ COG1410 group （P 〈0.05）. Compared with the sham group, the brain water content and the AQP-4 protein and mRNA expression levels in the SAH ＋ saline group and SAH ＋ COG1410 group were increased at each time point after SAH （P 〈 0.05 ）. The brain water content and the AQP-4 protein and mRNA expression levels in the SAH ＋ saline group and SAH ＋ COG1410 group were significantly increased in 1 d after SAH, reached the peak on 2 d, and then gradually declined （P 〈0.05）. Conclusion Administration of COG1410 significantly inhibits the cerebral edema via inhibition of AQP-4 expression.