PPARγ激动剂吡格列酮减少大鼠创伤性脑损伤后的神经损伤和胶质增殖  

PPARγ agonist pioglitazone attenuates cortical neuron lesion and gliosis in rat brain of post-traumatic injury

作　　者：乔保华[1] 高建新[1] 王芬[1] 邴国英[1,2] 

机构地区：[1]山东大学医学院生理学研究所,山东济南250012 [2]肯塔基大学医学院解剖和神经生物学系

出　　处：《中国病理生理杂志》2010年第5期912-916,共5页Chinese Journal of Pathophysiology

基　　金：山东省科技攻关计划资助项目(No.2006GG3202044)

摘　　要：目的:研究PPARγ激动剂吡格列酮(Pio)对大鼠创伤性脑损伤(TBI)所致皮层损伤的神经保护作用。方法:SD大鼠随机分为假手术组(sham组)、TBI后溶剂处理组(vehicle+TBI组)、TBI后Pio治疗组(Pio+TBI组)、TBI后Pio治疗加PPARγ拮抗剂组(Pio+T0070907+TBI组)。采用CCI方法制备大鼠TBI损伤模型;neutralred染色测定脑皮层损伤体积;脑组织切片NeuN、OX-42、GFAP免疫组化染色分别显示Pio对皮层损伤周围区神经元形态和数量变化以及对小胶质细胞和星形胶质细胞活化程度的影响。结果:大鼠CCI损伤引起皮层损伤周围区神经元数量大量丢失和小胶质细胞、星形胶质细胞过度活化增殖以及胶质瘢痕形成;Pio治疗显著减小了皮层损伤体积和神经元数量的减少,同时降低了小胶质细胞和星形胶质细胞的增殖活化;而T0070907逆转了Pio的上述作用。结论:Pio可能通过PPARγ抑制大鼠损伤皮层小胶质细胞和星形胶质细胞的过度增殖活化,降低炎性反应,从而减小了皮层损伤体积,增强了损伤神经元的存活和修复作用。AIM：To investigate the neuroprotective effect of pioglitazone （Pio）,a potent agonist of peroxi-some proliferator-activated receptor gamma （PPARγ）,on the traumatic brain injury （TBI） in rats. METHODS：SD rats were randomly divided into 4 groups：sham group,vehicle ＋ TBI group,Pio ＋ TBI group and Pio ＋ T0070907 ＋ TBI group. TBI was induced by the method of controlled cortical impact （CCI） injury. Neutral red staining technique was used to determine the cortical lesion volume. NeuN,GFAP and OX -42 were measured by immunohistochemical technique to evaluate the morphology of neurons,activation and infiltration of astrocytes and microglia at the edge of cortical lesion. RE-SULTS：CCI injury in rat elicited activation and proliferation of the astrocytes and microglia. The glial scar wall formation at the edge of cortical lesion,which was accompanied by the loss of neurons,was observed. Pio significantly reduced the cortical lesion volume,the activation and infiltration of the astrocytes and microglia,and the loss of pyramidal neurons at the edge of cortical lesion. T0070907,an antagonist of PPARγ,reversed the effects of Pio. CONCLUSION：Pioglitazone exerts a neuroprotective efficacy,attenuates the loss of neurons and cortical lesion volume following CCI injury by inhibiting the activation and infiltration of astrocytes and microglia,especially glial scar formation.

关 键 词：吡格列酮 创伤性脑损伤 神经元 神经胶质 过氧化物酶体增殖物激活受体Γ 

分 类 号：R332[医药卫生—人体生理学]