https://scholars.lib.ntu.edu.tw/handle/123456789/188397
Title: | 利用腺病毒轉殖增加環氧酵素一型及前列環素合成素的基因表現,對心臟缺血再灌流後心臟損傷之保護。 | Authors: | 陳錦澤 | Issue Date: | 2005 | Publisher: | 臺北市:國立臺灣大學醫學院內科 | Abstract: | 1 Prsotacyclin (PGI2) has been shown to prevent ischemic cardiac damage and stable PGI2 analogs are shown to exert cardioprotective actions by increasing blood flow, reducing platelet aggregation and direct cardiac protection In this study, we delivered the adenovirus containing COX-1/PGIS which is the key productive enzyme of PGI2 , using a catheter-based technique to investigate the signaling mechanism mediated by PGI2 in protection against cardiomyocyte apoptosis induced by acute ischemia/reperfusion. After adenovirus-mediated gene delivery, highly efficient and specific expression of green fluorescent protein, or recombinant human COX-1 and PGIS were identified in the left ventricle. Delivery of the PGI2 gene 5 days before ischemia/reperfusion attenuated myocardial apoptosis identified by in situ dUTP nick-end labeling and DNA laddering, and the effect was blocked by the cAMP antagonist which induced signal by PGI2 . Adv-COX-1/PGIS gene transfer increased phosphorylation of Akt but reduced and caspase-3 activities in the heart. The effects Adv-COX-1/PGIS gene transfer on phosphorylation of Akt and caspase-3 activities were blocked by LY294002(PI3 kinase inhibitor and by CAY(cAMP inhibitor).Furthermore, Adv-COX-1/PGIS gene transfer in cultured cardiomyocytes, also attenuated apoptosis induced by hypoxia/reoxygenation, which was accompanied by increased phospho-AKT and eNOS but reduced caspase-9 and caspase-3 activities. Phospho-AKT and caspase-3 activities were both blocked by Ad.DN-Akt andCAY and LY294002. These results indicate that Adv-COX-1/PGIS gene transfer protects against cardiomyocyte apoptosis induced by ischemia/reperfusion injury through the PI3 kinase-Akt-eNOS -caspase signaling pathway. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/23702 | Other Identifiers: | 932314B002203 | Rights: | 國立臺灣大學醫學院內科 |
Appears in Collections: | 醫學系 |
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932314B002203.pdf | 221.22 kB | Adobe PDF | View/Open |
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