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題 名 | Beneficial Effects of Tetramethylpyrazine, an Active Constituent of Chinese Herbs, on Rats with Endotoxemia=Tetramethylpyrazine具防禦敗血症之形成 |
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作 者 | 廖美惠; 吳錦楨; 顏茂雄; | 書刊名 | Proceedings of the National Science Council : Part B, Life Science |
卷 期 | 22:1 1998.01[民87.01] |
頁 次 | 頁46-54 |
分類號 | 418.1 |
關鍵詞 | 內毒素; 一氧化氮; 敗血症; Tetramethylpyrazine; Tumor necrosis factor-α; Nitric oxide; Lipopolysaccharide; Endotoxemia; |
語 文 | 英文(English) |
中文摘要 | Tetramethylpyrazine (中藥川芎的一主成份), 也是一種 phosphodiesterase 抑制劑,長期在中國大陸被用來改善心血管疾病。此研究動機在探討 tetramethylpyrazine 對內毒素在大鼠所引起的低血壓、血管低反應性和腫瘤壞死因子及一氧化氮的釋出之影響。 結果顯示, 大鼠經內毒素( 10mg/kg, i.v. )注射後會引起低血壓和心跳加快的現象, tetramethylpyrazine ( 10mg/kg,i.p. )可使血壓回升但卻使心跳有更加快的趨勢。內毒 素也會引起對 norepinephrine ( NE )的升壓(活體; 1 ug/kg,i.v. )和收縮(離體; 1uM )反應變差, 而大鼠在經 tetramethylpyrazine 預處理後,皆可部份改善此血管低反 應性的現象。 內毒素會導致血中腫瘤壞死因子及一氧化氮濃度的上升, 而此作用可被 tetramethylpyrazine 所部份拮抗。另外,tetramethylpyrazine 也可部份改善內毒素所引 發的早期低血壓作用, 由 acetylcholine ( ACh; 1 uM )的舒張反應證實 tetramethylpyrazine 並不影響內皮型一氧化氮合成酵素的活性(因 ACh 的舒張反應不受 tetramethylpyrazine 的影響)。因此,tetramethylpyrazine 改善內毒素所引起的低血壓 作用可能是經由減少循環因子(活化內皮型一氧化氮合成酵素)和腫瘤壞死因子的釋出進而 阻斷誘導型一氧化氮合成酵素的生成所致。 |
英文摘要 | Tetramethylpyrazine, an inhibitor of phosphodiesterase, has been widely used for treatment of cardiovascular diseases in China. Here, we investigate the effects of tetramethylpyrazine on hypotension, vascular hyporeactivity to norepinephrine (NE), release of tumor necrosis factor- α (TNF α ) and nitric oxide (NO) in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide, LPS). Male Wistar-Kyoto rats were anesthetized and instrumented for the measurement of mean arterial pressure (MAP) and heart rate (HR). Injection of LPS (10 mg/kg, i.v.) resulted in a fall in MAP and an increase of HR. In contrast, animals pretreated with tetramethylpyrazine (10 ug/kg, i.p. at 30 min prior to LPS) maintained a significantly higher MAP, but tachycardia was further enhanced at 60 min and 120 min when compared to rats given only LPS (LPS-rats). The pressor effect of NE (1 ug/kg, i.v.) was also significantly reduced after treatment of rats with LPS. Similarly, the thoracic aorta obtained from rats after in vivo studies showed a significant reduction in the contractile responses elicited by NE (1 uM). Pretreatment of LPS-rats with tetramethylpyrazine partially, but significantly, prevented this LPS-induced hyporeactivity to NE in vivo and ex vivo. The injection of LPS resulted in a significant increase in the plasma TNF α level at 60 min, whereas the effect of LPS on the plasma nitrate (an indicator of NO formation) level increased in a time-dependent manner. This increment of both TNF α and nitrate levels induced by LPS was significantly reduced in LPS-rats pretreated with tetramethylpyazine. The early hypotension caused by LPS was slightly, but significantly, prevented by pretreatment with tetramethylpyrazine, suggesting that tetramethylpyrazine affects the endothelial constitutive NOS (eNOS). This was examined by the effect of tetramethylpyrazine on acetylcholine (ACh, 1 uM)-induced relaxation in rats treated with tetramethylpyrazine for 4 h. However, tetramethylpyrazine had non significant effects on the ACh-induced relaxation, indicating that tetramethylpyrazine does not affect the activity of eNOS. Thus, tetramethylpyrazine attenuates the early hypotension and the delayed circulatory failure caused by endotoxin in the rat. These effects may be due to inhibition of the release of circulation factors and TNF α, which usually reveal synergism upon the induction of iNOS. |
本系統中英文摘要資訊取自各篇刊載內容。