重症颅脑损伤大鼠中SIRT1的表达情况及其对应激障碍的影响

Expression of silent information regulator related enzyme 1 and its effect on stress disorder in rats with severe traumatic brain injury

目的探讨基于p38分裂原激活蛋白激酶(p38MAPK)通路沉默信息调节因子相关酶1(SIRT1)表达水平在重症颅脑损伤大鼠中的变化及其对创伤后应激障碍(PTSD)的影响。方法 SD大鼠80只,留取15只作对照组,其余复制重症颅脑损伤大鼠模型。分为模型组、SIRT1过表达组、p38激动剂组。对照组仅制作假手术模型,SIRT1过表达组脑内注射过表达SIRT1慢病毒载体,p38激动剂组予以过表达SIRT1慢病毒载体+p38激动剂;模型组、对照组予以等体积生理盐水。评估各组大鼠创伤后第1、3及5天测试神经功能;高架十字迷宫实验评定创伤应激行为学;TTC法观察脑梗死面积;Western blotting检测梗死侧脑皮质中SIRT1、p38、p-p38蛋白的表达情况。结果从模型组、p38激动剂组、SIRT1过表达组到对照组,大鼠神经功能评分逐渐降低(P<0.05),进入开臂(和闭臂)次数逐渐增多,在开臂(和闭臂)停留时间逐渐延长(P<0.05)。模型组、SIRT1过表达组、p38激动剂组大鼠创伤后第1、3及5天脑梗死较明显,且随时间延长而加重;与模型组比较,SIRT1过表达组、p38激动剂组有所改善。从模型组、p38激动剂组、SIRT1过表达组到对照组,大鼠脑皮质SIRT1、p-p38蛋白相对表达量逐渐升高(P<0.05)。结论重症颅脑损伤大鼠脑皮质SIRT1表达下调,上调SIRT1可缓解PTSD,其机制可能与抑制p38信号通路有关。

Objective To investigate the change in the expression level of silent information regulator related enzyme 1(SIRT1) based on the p38 mitogen-activated protein kinase(p38 MAPK) signaling pathway in rats with severe traumatic brain injury and its effect on post-traumatic stress disorder(PTSD).Methods A total of 80 Sprague-Dawley rats were selected,among which 15 rats were established as control group and the rest of the rats were used to establish a rat model of severe traumatic brain injury and were then divided into model group,SIRT1 overexpression group,and p38 agonist group.The rats in the control group were given sham operation model,those in the SIRT1 overexpression group were given intracerebral injection of SIRT1 overexpression lentiviral vector,and those in the p38 agonist group were given SIRT1 overexpression lentiviral vector+p38 agonist;the rats in the model group and the control group were given an equal volume of normal saline.Neurological function was evaluated on days 1,3,and 5 after trauma;the elevated plus maze test was used to evaluate posttraumatic stress behavior;the TTC method was used to observe the area of cerebral infarction;Western blotting was used to measure the protein expression of SIRT1,p38,and p-p38 in the cerebral cortex at the ipsilateral side.Results Neurological score gradually decreased from the model group to the p38 agonist group,the SIRT1 overexpression group,and the control group(P <0.05),with gradual increases in the number of times of entering open arm(and closed arm) and the time spent in open arm(and closed arm)(P <0.05).The model group,the SIRT1 overexpression group,and the p38 agonist group had marked cerebral infarction on days 1,3,and 5 after trauma,which aggravated over time,and the SIRT1 overexpression group and the p38 agonist group had certain improvement compared with the model group.The relative protein expression of SIRT1 and p-p38 gradually increased from the model group to the p38 agonist group,the SIRT1 overexpression group,and the control group(P <0.05).Conclusion The expression of SIRT1 is downregulated in the cerebral cortex of rats with severe traumatic brain injury,and upregulation of SIRT1 can alleviate PTSD,possibly by inhibiting the p38 signaling pathway.