摘要
目的探讨贝前列素钠对全脑缺血/再灌注大鼠脑损伤的保护作用及对PGIS-PGI2-IP信号通路的影响。方法采用夹闭双侧颈总动脉合并低血压的方法建立大鼠全脑缺血/再灌注脑损伤模型,贝前列素钠(50、100μg·kg-1)术前30 min灌胃给药,水迷宫检测大鼠空间学习记忆能力,黄嘌呤氧化酶法、TBA法分别测定大鼠海马中SOD活性、MDA含量变化,ELISA测定大鼠海马PGI2含量,RT-PCR检测大鼠海马COX-2、PGIS与IP mRNA表达情况。结果与假手术组相比,全脑缺血/再灌注大鼠寻台潜伏期,寻台路径明显增加;SOD活性明显降低,MDA含量明显增加;PGI2含量明显增加,COX-2、PGIS、IP mRNA表达明显增加。与模型组相比较,贝前列素钠能明显改善大鼠空间学习记忆能力;升高海马SOD活性,降低MDA含量;明显降低海马PGI2含量,抑制海马COX-2、PGIS及IP mRNA的表达。结论贝前列素钠对全脑缺血/再灌注大鼠脑损伤具有明显的保护作用,其机制可能涉及调控PGIS-PGI2-IP信号通路平衡。
Aim To investigate the protective effect of beraprost sodium on global cerebral ischemia reperfu-sion （GCIR） injury in rats and its effects on PGIS-PGI2-IP signaling pathway. Methods The model of GCIR injury was established by bilateral common carot-id arteries occlusion and systemic hypotension in rats. Beraprost sodium（50 and 100 μg . kg-l） were intra-gastrically administered 30 min before the operation. Spatial learning and memory function of rats were ob- served by Morris Water Maze. The SOD activity and MDA content in rat hippocampus were evaluated by the method of xanthinoxidase and TBA respectively. The alteration of PGI2 content in rat hippocampus was measured by enzyme-linked immunosorbent assay. The changes of COX-2, PGIS and IP mRNA expression in rat hippocampus were detected by RT-PCR. Results Compared with those in the sham operation group, the spatial learning and memory function were notably im-paired in the ischemia group, the SOD activity obvi-ously decreased, the MDA and PGI2 content signifi-cantly increased, and the expression of COX-2, PGIS and IP mRNA in the hippocampus remarkably in-creased in the ischemia group. Beraprost sodium sig-nificantly improved the spatial learning and memory function of GCIR rats and remarkably blunted the de- crease of SOD activity, the increase of MDA content and PGI2 level in the hippocampus of GCIR rats. Bera- prost sodium also caused a significant down-regulation of COX-2, PGIS and IP mRNA expression in GCIR rats hippocampus. Conclusion Beraprost sodium has a protective effect on GCIR injury. The neuroprotective mechanism of beraprost sodium may involve in the reg-ulation of the balance of PGIS-PGI2-IP signal pathway.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第2期212-216,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金青年基金资助项目(No 81100905)
关键词
贝前列素钠
全脑缺血
再灌注
前列环素合酶
前列环素受体
前列环素
beraprost sodium
global cerebral ische-mia reperfusion
prostacyclin synthase
prostacyclinreceptor
prostacyclin
