摘要
目的探讨丁基苯酞(NBP)对创伤性脑损伤(TBI)模型大鼠神经功能的改善作用,以及对IRE1/XBP1信号通路的影响。方法将60只大鼠分为假手术组、模型组,以及NBP高、中、低剂量组(40,20,10mg/kg),各12只。采用改良Feeney自由落体撞击法复制大鼠TBI模型。建模后,各组大鼠腹腔注射相应药物,每天1次,持续7 d。评估大鼠神经功能缺损情况;测定大鼠脑组织含水量;采用TUNEL法评估大鼠脑细胞凋亡情况,并计算凋亡指数;采用酶联免疫吸附(ELISA)法测定大鼠脑组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)水平;采用聚合酶链式反应(PCR)法测定蛋白激酶C受体1(RACK1)、磷酸化IRE1(p-IRE1)、X-box结合蛋白1(XBP1)、葡萄糖调节蛋白78(GRP78)水平。结果与模型组比较,NBP高、中、低剂量组大鼠神经功能缺损评分,细胞凋亡指数,MDA,p-IRE1,XBP1,GRP78水平均显著降低;SOD和RACK1水平均显著升高,脑组织含水量显著增加(P <0.05)。结论 NBP对TBI模型大鼠神经功能有一定改善作用,其机制与抑制IRE1/XBP1信号通路有关。
Objective To investigate the effect of dl-3-n-butylphthalide(NBP)on the improvement of neurological function in rats with traumatic brain injury(TBI)and the effect on IRE1/XBP1 signaling pathway.Methods A total of 60 rats were divided into sham operation group,model group,NBP high-dose,medium-dose and low-dose groups(40,20,10 mg/kg),12 rats in each group.TBI model of rat was established by the modified Feeney’s free falling method.After modeling,rats in each group were intraperitoneally injected with corresponding drugs once a day for 7 d.The neurological deficit of rats was evaluated,the brain water content was measured,the apoptosis of brain cells was evaluated by the TUNEL method and the apoptosis index was calculated.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in brain homogenate were measured by enzyme-linked immunosorbent assay(ELISA).The levels of protein kinase C receptor 1(RACK1),phosphorylated IRE1(p-IRE1),X-box binding protein 1(XBP1)and glucose-regulated protein 78(GRP78)were determined by polymerase chain reaction(PCR).Results Compared with those in the model group,the neurological deficit score,apoptosis index,the levels of MDA,p-IRE1,XBP1 and GRP78 were significantly decreased,while the levels of SOD and RACK1 were significantly increased,and the brain water content was significantly increased in NBP high-dose,medium-dose and low-dose groups(P<0.05).Conclusion NBP has an improvement effect on the neurological function of TBI rats,and its mechanism may be related to its inhibition of IRE1/XBP1 signaling pathway.
作者
何云
桂水清
黄贤键
朱栋梁
HE Yun;GUI Shuiqing;HUANG Xianjian;ZHU Dongliang(Shenzhen Second People’s Hospital,Shenzhen,Guangdong,China 518035)
出处
《中国药业》
CAS
2021年第8期32-35,共4页
China Pharmaceuticals
基金
广东省深圳市科技计划项目[JCYJ20180228163034627]。
