Dl-3-n-butylphthalide improves functional recovery in rats with spinal cord injury by inhibiting endoplasmic reticulum stress-induced apoptosis

作者：He, Zili; Zhou, Yulong; Huang, Yan; Wang, Qingqing; Zheng, Binbin; Zhang, Hongyu; Li, Jiawei; Liu, Yanlong; Wu, Fenzan; Zhang, Xie; Tong, Songlin; Wang, Maofeng; Wang, Zhouguang; He, Huacheng; Xu, Huazi^*; Xiao, Jian^*

来源：American Journal of Translational Research, 2017, 9(3): 1075-1087.

• Dl-3-n-butylphthalide
• apoptosis
• ER stress
• spinal cord injury

Endoplasmic reticulum (ER) stress-induced apoptosis occurs in the spinal cord following traumatic spinal cord injury (SCI). Dl-3-n-butylphthalide (NBP) exerts an neuroprotective effects against both ischemic brain injury and neurodegenerative diseases; however, the relationship between ER stress-induced apoptosis and the therapeutic effect of NBP in SCI remains unclear. In this study, moderate spinal cord injuries were induced in Sprague-Dawley (SD) rats with a vascular clip. NBP was administered by oral (80 mg/kg/d) gavage 2 h before injury and then once daily for 28 d thereafter. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotion rating scale, the inclined plane test, and the footprint analysis. Neuronal cell death was examined by TUNEL staining at 7 days post-injury. ER stress and apoptosis-related proteins were quantified by immunofluorescence staining and western blotting both in vivo and in vitro. Our results showed that NBP significantly decreased spinal cord lesion cavity area and improved locomotor recovery in SD rats after SCI. NBP also decreased neuronal apoptosis and inhibited activation of the caspase 3 cascade. Upregulation of ER stress-related proteins, such as GRP78, ATF-6, ATF-4, PDI, XBP-1, and CHOP, was reversed by NBP treatment in SD rats with SCI. Similarly, NBP effectively ameliorated ER stress and apoptosis-related protein expression induced by incubation with thapsigargin (TG) in PC12 cells. Our findings demonstrate that NBP treatment alleviates secondary SCI by inhibiting ER stress-induced apoptosis, thereby promoting neurological and locomoter functional recovery.

• 出版日期2017
• 单位宁波市医疗中心李惠利医院; 温州医科大学