吡格列酮对创伤性脑损伤大鼠海马神经元的保护作用及机制探讨

Protective effects and mechanism of Pioglitazone on TBI-induced damage of hippocampus neurons in rats

目的研究吡格列酮对创伤性脑损伤(TBI)大鼠海马神经元和认知行为障碍的影响及其作用机制。方法将SD大鼠24只制成大鼠左侧脑皮层顶叶损伤模型,并分为假手术组(Sham组)、脑损伤溶剂注射组(Vehicle组)、吡格列酮治疗组(Pio组)、吡格列酮+过氧化物酶增殖因子活化受体γ(PPARγ)阻断剂(T0070907)组(Pio+Ant组)。采用Morris水迷宫实验观察大鼠记忆认知行为,对大鼠脑损伤第15天脑冠状切片进行小胶质细胞、星形胶质细胞和神经元的OX-42、GFAP、NeuN免疫组化染色,计数海马CA1、CA2及CA3区的细胞数量。结果 Vehicle组与Sham组比较,大鼠的潜伏期和游泳轨迹延长,海马神经元数量减少(P均<0.01),NeuN免疫染色变浅,小胶质和星形胶质细胞活化且数量增多(P均<0.01);Pio组与Vehicle组比较,大鼠潜伏期及游泳轨迹明显缩短(P均<0.05),神经元存活数量增多(P<0.05),NeuN蛋白表达增强,小胶质和星形胶质细胞反应减轻、数量减少(P均<0.05)。结论吡格列酮可以通过PPARγ通路减轻大鼠脑损伤导致的海马区炎性反应,保护神经元,提高TBI大鼠记忆认知功能。

Objective To investigate the effects and mechanism of Pioglitazone on traumatic brain injury（TBI）-induced deficits of learning memory ability and damage of hippocampus neurons in rats.Methods Left lobus parietalis damage models were made in 24 SD rats which were randomly divided into four groups： the Sham group,the Vehicle group,the Pio group and the Pio ＋Ant group.A Morris water maze was used to observe the changes of their learning memory behavior.On the 15th day the rats were sacrificed to take brain coronal frozen sections.NeuN,OX-42 and GFAP immunohistochemistry were used to stain neurons,microglia and astrocyte,and their numbers in hippocampus CA1,CA2 and CA3 areas were counted.Results The Morris water maze test indicated that compared with the Sham group the learning ability of the Vehicle group significantly dropped which was manifested as extension of latency（P0.01）and distance（P0.01）;the number of neurons was decreased（P0.01） and NeuN stain was light;and the numbers of microglias（P0.01） and astrocytes（P0.01） were increased.The Pio group had shorter latency and distance than the Vehicle group（both P0.05）;the number of surviving neurons was increased（P0.05） and expression of NeuN wasstrengthened;and the numbers of microglias（P0.05） and astrocytes were decreased（P0.05）.Conclusion According to the PPARγ pathway,Pioglitazone can alleviate the TBI-induced inflammatory reaction in the hippocampus and plays an important role in neuron protection and learning memory ability.