吡格列酮对大鼠颅脑损伤后核转录因子、肿瘤坏死因子-α和细胞凋亡的影响

Influence of pioglitazone on tissue nuclear transcription factor, tumor necrosis factor-α and cell apoptosis after traumatic brain injury in rats

目的探讨吡格列酮(PGZ)干预对大鼠颅脑损伤后脑组织中核转录因子NF-B、肿瘤坏死因子-(TNF-)和细胞凋亡的变化及其可能机制。方法 84只健康雄性SD大鼠随机分为PGZ组(=42)及对照组(=42),前者通过改良Feeney法建立颅脑损伤模型后立即予以腹腔注射PGZ10mg/kg,对照组则建立模型后予腹腔静脉注射0.9%氯化钠注射液2 ml/kg,以后各组分别每24小时腹腔注射一次等量PGZ或0.9%氯化钠注射液,直至动物被处死,根据伤后处死时间随机分为1h、3h、6h、12h、24h、3d和7d共7个亚组,每亚组各6只。取损伤灶周围组织采用免疫组织化学方法检测并比较挫伤灶周围脑组织中NF-B及TNF-蛋白表达情况,同时采用TUNEL法观察并比较脑挫伤灶周围细胞凋亡情况。结果 PGZ组NF-B及TNF-蛋白表达水平较对照组均明显下降(均<0.05)。以NF-B含量水平为自变量,TNF-含量水平为应变量,回归方程Y(PGZ组)=-0.432+0.271X,2=0.947(<0.01);Y(对照组)=-4.168+0.748X,2=0.961(<0.01)。结论颅脑损伤后PGZ可能通过降低NF-B活性,控制炎症反应,减少细胞凋亡,从而发挥对颅脑损伤后的神经细胞发挥保护作用。

Objective To investigate the changes of tissue nuclear transcription factor （NF-KB）, tumor necrosis factor-α （TNF-α） and cell apoptosis after traumatic brain injury and the influence ofpioglitazone on these para-meters in rats. Methods Eighty-four male SD rats were randomly divided into two groups randomly： pioglitazone group （n=42） and the control group （n=42）.The pioglitazone group were induced by improved Feeney method and were received abdominal injections of pioglitazone （10 mg/kg） immediately after injury, and the control group were received abdominal injections of sodium chloride injection （2 ml/kg） immediately alter injury and one time everyday until the rats was killed. Each group was divided into seven subgroups by sacrificed time after injury, 1 h, 3 h, 6 h, 12 h, 24 h, 3 d, and 7 d group, each subgroup got six rats. Each subgroup were randomly selected three rats after being killed, detected the expression of NF-κB and TNF- α of tissues around contusion by immunohistochemical methods, while TUNEL method was used to observe the cell apoptosis after brain contusion.Results The expressions of NF-κB and TNF-α in each pioglitazone group were significantly decreased compared with the control group （P 〈 0.05）, and they showed significant positive correlations in both groups （P 〈 0.01）. At the same time, the number ofapoptotic cells was decreasing （P 〈 0.05）.Conclusions Pioglitazone can protect ofneurocytes through the route of relieving inflammation response, reducing the change of secondary brain injury after traumatic brain injury and decreasing neural cell apoptosis.