Potential advantages of Chinese medicine Taohong Siwu Decoction (桃红四物汤) combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats

Ting Lin Yen, Eng Thiam Ong, Kuan Hung Lin, Chao Chien Chang, Thanasekaran Jayakumar, Song Chow Lin, Tsorng Han Fong, Joen Rong Sheu

研究成果: 雜誌貢獻文章同行評審

摘要

OBJECTIVE: To investigate whether combination treatment with Taohong Siwu Decoction (, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.

METHOD: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed.

RESULTS: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (P<0.01). A combined treatment of rt-PA (4 mg/kg) with TSD [0.7 g/(kg·day)] significantly increased cerebral blood flow in a time (100 and 120 min) dependent manner (P<0.05). Interestingly, despite treatment of rt-PA (4 mg/kg) alone significantly reduced the expressions of HIF-1α, TNF-α, and iNOS in ischemic regions, reduction of these expressions were more potentiated when combined with TSD (P<0.05). Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared with the MCAO group (P<0.01).

CONCLUSIONS: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.

原文英語
頁(從 - 到)1-14
頁數14
期刊Chinese Journal of Integrative Medicine
DOIs
出版狀態打印前電子出版 - 九月 24 2014

ASJC Scopus subject areas

  • 補充和替代醫學
  • 藥學(醫學)

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