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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 effect of pioglitazone on hippocampal neurons and cognitive impairment after traumatic brain injury (TBI) in rats and its mechanism. Methods Twenty-four Sprague Dawley rats were divided into Sham group, Vehicle group, Pioglitazone group (Pio group), Pioglitazone group + Peroxisome proliferator-activated receptor γ (PPARγ) blocker (T0070907) group (Pio + Ant group). Morris water maze test was used to observe the cognitive behavior of rats. OX-42, GFAP and NeuN immunohistochemical staining of microglia, astrocytes and neurons were performed on the 15th day after brain injury in rats , Counting the number of cells in hippocampal CA1, CA2 and CA3 area. Results Compared with Sham group, vehicle latency and swimming path in Vehicle group were prolonged, the number of neurons in hippocampus was decreased (P <0.01), NeuN immunostaining was shallow, and microglia and astrocyte were activated (P (P <0.05). The number of neurons increased (P <0.05), the expression of NeuN protein increased, but the microglia and astrocytes Mitochondrial response reduced, the number decreased (P <0.05). Conclusion Pioglitazone can attenuate the inflammatory response in the hippocampus induced by brain injury in rats through PPARγ pathway, protect the neurons and improve the cognitive function of memory in TBI rats.