Neuroprotective effect of dauricine after transient middle cerebral artery occlusion in rats: involvement of Bcl-2 family proteins.
Previous studies have shown that the bisbenzyl isoquinoline alkaloid dauricine can protect the brain against ischemic damage. We investigated here whether dauricine could inhibit neuronal apoptosis and modulate Bcl-2 family protein levels in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats underwent a 60 min temporary occlusion of the middle cerebral artery (MCAO). Two doses of dauricine (5 and 10 mg/kg as low and high dose respectively) were administered intraperitoneally at 1 hour after MCAO. After neurological deficits were assessed at 3 hours and 24 hours of reperfusion, rats were killed and brain samples were collected. Apoptotic changes were evaluated by TUNEL method. The immunohistochemistry and Western blot were used to assess the protein expressions of Bcl-2 and Bax. RT-PCR was used to determine Bcl-2 and Bax mRNA expressions. Dauricine (5 and 10 mg/kg) treatment improved neurological deficits, diminished DNA fragmentation, increased Bcl-2 expression and reduced Bax expression in the penumbra. The infarct-reducing effects of dauricine may be due, in part, to the inhibition of apoptotic cell death via modulation Bcl-2 family protein in the penumbra.
Yang
Xiao-Yan
XY
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liu
Qiang-Ni
QN
Zhang
Li
L
Jiang
Shi-Qin
SQ
Gong
Pei-Li
PL
D000818:Animals; D017209:Apoptosis; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D044182:Benzylisoquinolines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; C035934:dauricine