The therapeutic effect of (DL)-3-n-butylphthalide in rats with chronic cerebral hypoperfusion through downregulation of amyloid precursor protein and matrix metalloproteinase-2.
OBJECTIVE
To investigate the therapeutic effect of DL-3-n-butylphthalide (DL-NBP) in rats with chronic cerebral hypoperfusion.


METHODS
Chronic cerebral hypoperfusion was modelled by bilateral permanent occlusion of common carotid arteries in Wistar rats. The therapeutic effect  of DL-NBP in hypoperfused rats was evaluated using the Morris water maze task. The levels and deposition of matrix metalloproteinase (MMP) and the amyloid precursor protein β-amyloid 40 (Aβ40) were measured by Western blot analysis and immunohistochemistry in the cerebral cortex  and hippocampus.


RESULTS
Treatment with DL-NBP significantly improved the learning and memory ability of hypoperfused rats. Western blot analysis indicated that, in comparison with the sham-operated control group, protein levels of Aβ40 and MMP-2 were significantly increased in the cerebral  cortex of hypoperfused rats, and treatment with DL-NBP prevented this hypoperfusion-induced increase in Aβ40 and MMP-2. Immunohistochemical analysis showed that Aβ40 and MMP-2 were deposited in venous endothelial cells at day 3 and in arterial endothelial cells at day 14 after hypoperfusion.


CONCLUSIONS
This study indicated that DL-NBP has therapeutic effects on chronic cerebral hypoperfusion and provided a useful insight into the potential molecular mechanisms underlying the therapeutic effect of DL-NBP in chronic cerebral hypoperfusion.
Department of Neurology, Beijing Military General Hospital, Beijing, China.
W
W
Wei
W
W
Zhang
Y
Y
Huang
Y
Y
Li
G
G
Zhu
F
F
Chen
J
J
Li
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002908:Chronic Disease; D015536:Down-Regulation; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D018782:Maze Learning; D051381:Rats; D017208:Rats, Wistar
D016564:Amyloid beta-Protein Precursor; D001572:Benzofurans; C027125:3-n-butylphthalide; D020778:Matrix Metalloproteinase 2