PMID- 28386335
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 9
IP  - 3
DP  - 2017
TI  - Dl-3-n-butylphthalide improves functional recovery in rats with spinal cord 
      injury by inhibiting endoplasmic reticulum stress-induced apoptosis.
PG  - 1075-1087
AB  - 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.
FAU - He, Zili
AU  - He Z
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      UniversityWenzhou 325035, Zhejiang, PR China; Molecular Pharmacology Research 
      Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, 
      PR China.
FAU - Zhou, Yulong
AU  - Zhou Y
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      UniversityWenzhou 325035, Zhejiang, PR China; Molecular Pharmacology Research 
      Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, 
      PR China.
FAU - Huang, Yan
AU  - Huang Y
AD  - Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Wang, Qingqing
AU  - Wang Q
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Zheng, Binbin
AU  - Zheng B
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      UniversityWenzhou 325035, Zhejiang, PR China; Department of Orthopaedics, Taizhou 
      Hospital, Wenzhou Medical UniversityLinhai 317000, Zhejiang, PR China.
FAU - Zhang, Hongyu
AU  - Zhang H
AD  - Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical 
      UniversityWenzhou 325035, Zhejiang, PR China; Department of Biomedical Sciences 
      Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical UniversityDongyang 
      322100, Zhejiang, PR China.
FAU - Li, Jiawei
AU  - Li J
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Liu, Yanlong
AU  - Liu Y
AD  - Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Wu, Fenzan
AU  - Wu F
AD  - Department of Neurosurgery, Affiliated Cixi People's Hospital, Wenzhou Medical 
      University Ningbo 315300, PR China.
FAU - Zhang, Xie
AU  - Zhang X
AD  - Department of Gastroenterology, Ningbo Medical Treatment Center Li Hui-Li 
      Hospital Ningbo 315040, PR China.
FAU - Tong, Songlin
AU  - Tong S
AD  - Department of Neurosurgery, Affiliated Cixi People's Hospital, Wenzhou Medical 
      University Ningbo 315300, PR China.
FAU - Wang, Maofeng
AU  - Wang M
AD  - Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of 
      Wenzhou Medical University Dongyang 322100, Zhejiang, PR China.
FAU - Wang, Zhouguang
AU  - Wang Z
AD  - Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - He, Huacheng
AU  - He H
AD  - Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Xu, Huazi
AU  - Xu H
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      University Wenzhou 325035, Zhejiang, PR China.
FAU - Xiao, Jian
AU  - Xiao J
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical 
      UniversityWenzhou 325035, Zhejiang, PR China; Molecular Pharmacology Research 
      Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, 
      PR China.
LA  - eng
PT  - Journal Article
DEP - 20170315
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5376000
OTO - NOTNLM
OT  - Dl-3-n-butylphthalide
OT  - ER stress
OT  - apoptosis
OT  - spinal cord injury
EDAT- 2017/04/08 06:00
MHDA- 2017/04/08 06:01
PMCR- 2017/03/15
CRDT- 2017/04/08 06:00
PHST- 2016/07/04 00:00 [received]
PHST- 2016/12/29 00:00 [accepted]
PHST- 2017/04/08 06:00 [entrez]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2017/04/08 06:01 [medline]
PHST- 2017/03/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2017 Mar 15;9(3):1075-1087. eCollection 2017.