吡格列酮对脂多糖所致大鼠学习记忆障碍的改善作用及其机制

目的研究吡格列酮(Pioglitazone,Pio)对脂多糖引起的大鼠学习记忆障碍和海马CA1区锥体神经元损伤的保护作用。方法大鼠灌胃给予Pio(408、0 mg/kg)3周,脑室内注射LPS(5、30μg),2 d后进行Mor-ris水迷宫定位航行实验,连续训练5 d,第6天进行空间探索实验。行为学实验后,取脑组织,制成石蜡切片,进行尼氏(Nissl)染色和胶质纤维酸蛋白(Glial fibrillary acidic protein,GFAP)免疫组织化学染色,研究海马CA1区锥体神经元形态学改变和星型胶质细胞的活化浸润情况。结果脑内注射LPS可以引起大鼠学习和记忆障碍,表现为大鼠逃避潜伏期较对照组明显延长,大鼠在平台所在象限游泳距离百分比明显较对照组低,这些行为学改变伴随海马CA1区星型胶质细胞和锥体神经元的损伤。治疗组LPS所致的学习记忆损伤减轻,Pio能明显减轻海马CA1区锥体神经元的损伤和星型胶质细胞的浸润。结论吡格列酮能对抗LPS引起的锥体神经元的损伤和星型胶质细胞的活化浸润,从而改善大鼠的学习记忆能力。

Protective effects of pioglitazone on LPS-induced cognitive deficits and damages of neurons in rats

Objective To study the protective effects of pioglitazone on LPS-induced cognitive deficits and damages of hippocampal CA1 pyramidal neurons in rats.Methods Rats were given Pio(40,80 mg/kg) with ig method for 3 weeks,then they were injected LPS.Two days later,Morris water maze was used to measure the spatial learning and memory ability of rats.After behavior test,Nissl staining and immunohistochemical technique(for GFAP) were employed to determine the morphology of pyramidal neurons and astrocyte infiltration in hippocampal CA1.Results Intracere broventricular injection of LPS in rats resulted in spatial learning and memory impairments which shown by longer escape latency and decreased the percentage of swimming distant in the target quadrant.These behavioral dysfunction were accompanied by injury of astrocyte and pyramidal neurons in hippocampal CA1.Oral administration of Pio(40,80 mg/kg) markedly alleviated the memory impairment and the damage of hippocampal CA1 pyramidal neurons.Conclusion Pio can improve the learning and memory ability of rats impaired by LPS through suppressions of inflammatory response and protection of hippocampal CA1 pyramidal neurons.