4-苯基丁酸抑制PERK/eIF2α信号通路缓解大鼠脊髓损伤内质网氧化应激反应  

4-PBA alleviates endoreticulum stress via inhibition of PERK/eIF2α signaling pathway in spinal cord injury rat

作　　者：刘威[1] 张绍昆[1] 牛丰[1] 赵松[1] 陈克研 闫明[1] LIU Wei;ZHANG Shao-kun;NIU Feng;ZHAO Song;CHEN Ke-yan;YAN Ming(Department of Spinal Surgery,the First Hospital of Jilin University,Changchun 130021;Department of Experimental Animals,China Medical University,Shenyang 110122,China)

机构地区：[1]吉林大学第一医院脊柱外科,吉林长春130021 [2]中国医科大学实验动物部,辽宁沈阳110122

出　　处：《解剖科学进展》2021年第1期1-4,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180551091)。

摘　　要：目的探讨4-苯基丁酸对脊髓损伤大鼠的作用和可能机制。方法采用Allen’s法操作方法建立脊髓损伤模型,将SD大鼠分为假手术组(Sham组)、模型组(SCI组)和4-苯基丁酸钠治疗组(4-PBA组);对三组大鼠进行脊髓运动功能(BBB)的评分;应用HE染色检测各组大鼠脊髓的损伤情况;采用ELISA检测各组大鼠血清中MDA、CAT、SOD、GSH-Px等蛋白的表达情况;应用免疫组织化学检测内质网应激蛋白GRP78、ATF4和CHOP的表达水平;Western blot法检测PERK、eIF2α、ATF4蛋白的表达水平。结果 4-苯基丁酸明显降低中性粒细胞的浸润程度,减少脊髓内GRP78、ATF4和CHOP表达水平,BBB评分在各个时间点明显升高,上调血清SOD、CAT,GSH-Pxe和IF2α的表达水平,下调MDA和ATF4的表达水平(P<0.05),p-PERK/PERK的表达无明显变化。结论 4-苯基丁酸缓解线粒体氧化应激从而减轻大鼠脊髓损伤与抑制PERK/eIF2α信号通路相关。Objective To investigate the effect of 4-PBA on spinal cord injury rats and its possible mechanism. Methods SD rats were divided into sham group, SCI(spinal cord injury) group and 4-PBA group. Basso beattie bresnahan(BBB) was used to evaluate the motor function of rats. HE staining was used to detect the spinal cord injury, the levels of MDA, CAT, SOD and GSH-Px in serum were detected by ELISA. The expressions of GRP78, ATF4 and CHOP were detected by immunohistochemistry, and the expressions of PERK, eIF2α and ATF4 were detected by Western blot. Results 4-PBA significantly reduced the infiltration of neutrophils, downregulated the expression levels of GRP78, ATF4 and CHOP in spinal cord and MDA value, upregulated BBB score and contents of SOD, CAT and GSH-Px and the expression level of eIF2 in serum, but decreased the level of ATF4(P<0.05). Conclusion 4-PBA can activate PERK/eIF2α signal pathway and inhibite ERS to reduce spinal cord injury in rats.

关 键 词：PERK/eIF2α通路 脊髓损伤 内质网应激 4-苯基丁酸 SD大鼠 

分 类 号：R651.2[医药卫生—外科学]