贝前列素钠对慢性铝过负荷大鼠皮层损伤的作用及机制

摘要

目的：探讨贝前列素钠对慢性铝过负荷大鼠皮层损伤的作用及对PGIS-IP信号通路的影响。方法将75只 SD大鼠随机分为5组,即正常对照组、慢性铝过负荷模型组、贝前列素钠低(6μg·kg-1)、中(12μg·kg-1)、高(24μg· kg-1)剂量组。采用葡萄糖酸铝( Al3+200 mg·kg-1·d-1)灌胃大鼠,每周5 d,连续20周,建立慢性铝过负荷损伤模型。贝前列素钠(6、12、24μg·kg-1)组,在每次给予葡萄糖酸铝2 h后,灌胃给予贝前列素钠。20周后, Morris水迷宫测定大鼠空间学习记忆能力；HE染色观察大鼠皮层神经元形态结构变化；生化酶学法测定大鼠皮层SOD活性和MDA含量变化；ELISA法检测大鼠皮层6-k-PGF1α含量；qRT-PCR检测大鼠皮层PGIS、IP mRNA表达情况；Western blot检测大鼠皮层IP蛋白表达情况。结果铝过负荷模型组与正常对照组相比,大鼠的寻台潜伏期延长( P<0．01)；皮层神经元出现明显的核固缩；SOD活性降低(P<0．01),MDA含量增加(P<0．05)；6-k-PGF1α含量升高(P<0．01)；皮层PGIS、IP mRNA表达增高( P <0．01)；皮层 IP 蛋白表达增高( P <0．05)。贝前列素钠组与铝过负荷模型组相比,大鼠的寻台潜伏期明显缩短(P<0．01)；皮层神经元损伤明显减轻；SOD活性升高(P<0．01),MDA含量降低(P<0．01)；6-k-PGF1α含量下降(P<0．05)；皮层PGIS、IP mRNA表达明显降低(P<0.05、P <0．01)；皮层 IP 蛋白表达也明显降低( P <0．05)。结论贝前列素钠对慢性铝过负荷大鼠皮层神经元有明显保护作用,其机制可能涉及PGIS-IP信号通路。%Aim To investigate the protective effects of beraprost sodium on cerebral cortical neuron injury in chronic aluminum-overload rats and its effects on PGIS-IP signaling pathway. Methods 75 SD rats were randomized into five groups: normal control group, chronic aluminum-overload group ( model group) and beraprost sodium groups-low dose (6 μg· kg-1 ), medium dose ( 12 μg · kg-1 ) and high dose (24 μg·kg-1). Aluminum gluconate (Al3+ 200 mg ·kg-1 d-1, once a day, 5d a week, for 20 weeks, p. o. ) was administered to rats of cerebral damage model. The rats of experimental groups were concomi-tantly treated with beraprost sodium ( p. o. ) daily for 20 weeks. After the model was built successfully, the spatial learning and memory( SLM) function was done by Morris water maze. The cortical neurons damage was detected by HE staining, SOD activities and MDA contents. The 6-k-PGF1α levels in cortex were meas-ured by ELISA. The expressions of PGIS, IP mRNA and IP protein were also studied. Results Compared with the rats of normal control group, the SLM function was significantly impaired ( P<0. 01 ) and considera-ble karyopycnosis was observed in model group rats. The SOD activities were weakened ( P <0. 01 ), the MDA contents increased ( P<0. 05 ) and the levels of 6-k-PGF1α raised significantly ( P <0. 01). The ex-pressions of PGIS and IP mRNA in the rats cortex obvi-ously increased ( P<0. 01 ), so did the expression of IP protein(P<0. 05). Compared with the rats of mod-el group, the SLM function of rats in experimental groups decreased significantly ( P<0. 01 ) and damage of cortical neurons reduced remarkably. The SOD ac-tivities increased ( P <0. 01 ) and the MDA contents decreased ( P <0. 01). Besides, the content of 6-k-PGF1α, the expressions of PGIS mRNA and IP protein in the rats cortex decreased significantly ( P<0. 05 ) as well as IP mRNA ( P<0. 01). Conclusion Our re-sults demonstrate that in cerebral cortical neuron of chronic aluminum-overload rats, beraprost sodium has notably protective effects and the mechanism might be related to PGIS-IP signaling pathway.