Abstract
OBJECTIVE To investigate the effects of puerarin(Pur)on the apoptosis and regulation of XIAP expression induced by cerebral ischemia. METHODS Male SD rats were treated with 50 min middle cerebral artery occlusion(MCAO)followed by reperfusion for 24 h. Pur(50, 100 mg·kg-1,ip)was administrated at the onset of MCAO. Twenty-four hours after reperfusion, neurological deficits were assessed in Pur-and vehicle-treated rats. The infarct volume and edema ratios were evaluated from TTC stained brain slices. Apoptosis and necrosis were measured using flow cytometric analysis of Annexin-V and PI labeling cells. Furthermore, the expression of the X-chromosome-linked inhibitor of apoptosis protein(XIAP) was analyzed by RT-PCR. RESULTS Pur(100 mg·kg-1)obviously attenuated ischemia-induced edema and neurological deficits, and markedly reduced infarction(P<0.05,P<0.01). The percentages of apoptosis and necrosis in dorsolateral cortex were significantly decreased(P<0.01 and P<0.05)following treatment with Pur(100 mg·kg-1)in MCAO rats. Furthermore, caspase-3 activity, as a biochemical marker of apoptosis, was significantly inhibited, and XIAP mRNA was significantly up-regulated by Pur(100 mg·kg-1)in the dorsolateral cortex of MCAO rats. CONCLUTION The neuroprotection of puerarin against cerebral ischemia is associated with the regulation of XIAP and the inhibition of apoptosis.
Key words
puerarin /
cerebral ischemia /
apoptosis /
caspase-3 activity
{{custom_keyword}} /
Cite this article
Download Citations
XU Xio-hong;CHEN Yu;ZHENG Xio-xing.
Effects of Puerarin on Neuronal Apoptosis Induced by Cerebral Ischemia in Rats [J]. Chinese Pharmaceutical Journal, 2006, 41(21): 1628-1631
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] WANG L Y，ZHAO A，WANG F， et al. Protective effect of puerarin on acute cerebral ischemia in rats [J] . Chin Mater Med J(中国中药杂志)，1997，22（12）：752-754.
[2] SANG H F， ZHANG Y M，XU L X， et al. Protective effect of puerarin on spinal cord injury resulting from ischemia and reperfusion in rabbits[J] . Fourth Mil Med Univ J（第四军医大学学报），2001，22（5）：414-417.
[3] DONG L P，WANG T Y. Effects of puerarin against glutamate excitotoxicity on cultured mouse cerebral cortical neurons[J] . Acta Pharmacol Sin(中国药理学报)，1998，19： 339-342.
[4] DONG L P，HAN M，YUAN F，et al. The protective effect of puerarin on cultured rat cerebral cortical astrocytes[J] . Chin Appl Physicol J（中国应用生理学杂志），2001，17（2）：141-143.
[5] Trapp T，Korhonen L，Besselmann M，et al. Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia[J] . Mol Celr Neurosci，2003，23：302-313.
[6] LeBlanc A. Natural cellular inhibitors of caspases[J] . Prog Neuro psychopharmacol Biol Psychiatry，2003，27：215-229.
[7] XU D，Bureau Y，McIntyre D C，et al. Attenuation of ischemia-induced cellular and behavioral deficits by X-chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus[J] .J Neurosci，1999，19：5026-5033.
[8] Longa E Z，Weinstein P R，Carlson S，et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J] .Stroke， 1989，20：84-91.
[9] Prakasa B P，Yoshida Y，SU M，et al. Immunohistochemical expression of Bcl-2，Bax and cytochrome C following focal cerebral ischemia and effect of hypothermia in rat[J] . Neurosci Lett， 2000，291：196-200.
[10] Paxinos G，Watson C.The Rat Brain in Stereotaxic Coordinates[M] . 4th ed，San Diego：Academic Press，1998.
[11] LEE S H，KIM M，KIM Y J，et al. Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats[J] . Brain Res，2002，956：14-23.
[12] Benchoua A，Guegan C，Couriaud C，et al. Specific caspase pathways are activated in two stages of cerebral infarction[J] . J Neurosci，2001，21：7127-7134.
[13] YANG J，Klaidman L K，CHANG M L，et al. Nicotinamide therapy protects against both necrosis and apoptosis in a stroke model[J] . Pharmacol Biochem Behav，2002，73：901-910.
[14] Hatfield R H，Gill R，Brazell C. The dose-response relationship and therapeutic window for dizocilpine(MK-801)in a rat focal ischemia model[J] . Eur J Pharmacol，1992，216： 1-7.
[15] Korhonen L，Belluardo N，Lindholm D. Regulation of X chromosome-linked inhibitor of apoptosis protein in kainic acid induced neuronal death in the rat hippocampus[J] . Mol Cell Neurosci，2001，17：364-372.
[16] Love S. Apoptosis and brain ischemia[J] . Prog Neuropsychopharmacol Biol Psychiatry，2003，27：267-282.
[17] XU X H，ZHAO T Q. Effects of puerarin on memory behavior and lipid peroxidation in aging mice[J] . Acta Pharmacol Sin(中国药理学报)，2002，23： 587-590.
{{custom_fnGroup.title_en}}
Footnotes
{{custom_fn.content}}
