PPARγ激动剂吡格列酮对创伤性脑损伤后神经细胞凋亡及ICMA-1表达的影响

Effects of peroxisome proliferator-activated receptor gamma agonist pioglitazone on neurocyte apoptosis and expression of ICAM-1 after traumatic brain injury

目的观察过氧化物酶体增殖物激活受体γ（peroxisome proliferator—activated receptor-γ,PPARγ）激动剂吡格列酮对大鼠创伤性脑损伤（traumaticbraininjury，TBI）后迟发性神经元死亡、细胞凋亡及细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1）表达的影响。方法将36只SD大鼠按随机数字表法分为假致伤组、对照组和吡格列酮治疗组，每组12只。采用改良的Feeney法制作脑创伤模型，治疗组采用吡格列酮（10mS／kg）灌胃，假致伤组和对照组用等量体积分数0．2％二甲基亚砜灌胃。致伤后48h取脑组织，石蜡切片，分别行Nissl、TUNEL染色和ICAM—l免疫组化测定，观察迟发性神经元死亡、神经细胞凋亡程度及ICAM-1表达。结果（1）治疗组尼氏体脱失细胞率为（38．59±1．97）％，明显低于对照组的（51．25±4．01）％（P〈0．05），高于假致伤组的（8．654-1．23）％（P〈0．01）；（2）治疗组神经细胞凋亡计数为31．67±4．76，明显低于对照组45．33±4．68（P〈0．05），高于假致伤组16．83±2．04（P〈0．01）；（3）治疗组ICAM-1表达阳性细胞的平均吸光度值为0．26±0．04，明显低于对照组0．31±0．04（P〈0．05），高于假致伤组0．10±0．02（P〈0．01）。结论PPARγ激动剂吡格列酮能减少TBI后的神经细胞凋亡，保护神经元；其抑制ICAM-1的表达可能是其抑制炎症反应、发挥神经保护作用的机制之一。

Objective To investigate the effects of peroxisome proliferator-activated receptor gamma （PPAR＇y） agonist pioglitazone on delayed neuronal death, apoptosis of neurocytes, and expression of intercellular adhesion molecule-1 （ ICAM-1 ） following traumatic brain injury （ TBI ） in rats. Methods Thirty-six Sprague-Dawley rats were randomized into sham injury group, control group and pioglitazone treatment group, with 12 rats in each group. TBI model was established by modified Fceney method. Treatment group received intragastric administration of pioglitazone at a dosage of 10 mg/kg, and the sham injury group and the control group were lavaged with isometric O. 2% dimethyl sulphoxide. Paraffin sections of brain tissues collected at 48 hours after TBI were employed to observe delayed neuronal death, apoptosis of neurocytes and expression of ICAM-l by Nissl staining, TUNEL staining and immunochemistry respectively. Results （ 1 ） Cell loss rate of Nissl body in the treatment group [ （38.59 ± 1.97） % ] was significantly lower than that of the control group [ （51.25 ±4.01 ）% ] （P 〈0.05） , but was higher than that of the sham injury group [ （8.65 ± 1.23）% ] （P 〈0.01 ）. （2） The number of apoptotie neuro- eytes of the treatment group （31.67 ± 4.76） was significantly lower than that of the control group （45.33 ± 4.68 ） （ P 〈 0.05 ） , but was higher than that of the sham injury group （ 16.83 ± 2.04） （ P 〈 0.01 ）. （3） The mean optical degree of ICAM-1 positive expression of the treatment group （ 0.26 ± 0.04 ） was significantly lower than that of the control group （0.31 ± 0.04） （P 〈 0.05 ） , but was higher than that of the sham injury group （0.10± 0.02） （ P 〈 0.01 ）. Conclusions The PPATRγ agonist pioglitazone can reduce the apoptosis of neurocytes and protect neurons after TBI. Meanwhile, its suppression of ICAM-1 expression is probably a mechanism of the suppression of inflammatory reaction and neural protection.