一種菁光敏染料 Platonin的心血管藥理學：從分子觀點著手

Cardiovascular Pharmacology and Molecular Targets of Platonin, a Cyanine Photosensitizing Dye

Platonin（4, 4′, 4″-thrimethyl-3, 3′, 3″-triheptyl-7- [2″-thia-zolyl] -2, 2′- trimethinethiazolocyanine-3-3″-diiodide），一種菁光敏染料和強效的抗氧化劑，具有有效活性氧（ROS）和氮（RNS）的清除能力 . 它還具有強效的免疫調節作用，目前用於治療免疫疾病，尤其是類風濕性關節炎。此外，它具有顯著的抗發炎能力，改善敗血症大鼠的死亡率和循環衰竭。以前的研究資料也顯示，Platonin 可以有效地抑制內毒素有關的炎症分子，如白血球介素 1β，白血球介素 6，腫瘤壞死因子 α（TNF-α）和誘導型一氧化氮合酶（iNOS）。我們以往的研究顯示，Platonin 具有在熱中暑期間，可以抑制熱原釋放、組織損傷及缺血、及肺的缺血再灌注損傷和它證實也可以改善大鼠的皮膚移植物存活的影響。目前尚未有這種化合物的心血管藥理學的綜述。因此，我們綜論一些獨特的 platonin 的心血管藥理作用。並探討核因子活化 B 細胞 κ 輕鏈增強子，胞外信號調節激酶，一氧化氮／一氧化氮合酶之間的訊息傳遞，這些都被認為是在未來心血管疾病有希望的分子標靶治療。

Platonin (4,4’,4’’-Trimethyl-3,3’,3’’-Trihepthyl-7-(2’’-thiazolyl)-2,2’,-Trimethine Thi-azolocyanine-3,3’’-Diiodide), is a cyanine photosensitizing dye and has potent antioxidant scavenging ability for reactive oxygen (ROS) and reactive nitrogen species (RNS). It al-so has potent immunomodulating effect and is being developed for the treatment of immune diseases, especially rheumatoid arthritis. In addition, platonin shows anti-inflammatoryactiv-ity, improves circulatory insufficienc, and reduces mortality in septic rats. Previous data also showed that platonin inhibited endotoxin-induced up-regulation of inflammatorymolecules (e.g. interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and inducible nitric ox-ide synthase (iNOS)). Our previous studies demonstrated that platonin has inhibitory effects on pyrogen release, tissue damage, and ischemic during heatstroke in rats . Platonin also sup-presses ischemia reperfusion injury in lungs and improves the survival of skin allografts in rats. However, there is no organized and precise review about the cardiovascular pharmacol-ogy of platonin. Therefore, we here summarize some interesting and unique cardiovascular pharmacological actions of platonin. Furthermore, this review discusses the signaling cas-cades targeted by platonin which include those mediated by nuclear factor-kB (NF-kB) and mitogen-activated protein kinases (MAPKs), and NO/NOS. NF-kB and MAPKs are consid-ered promising molecular targets for the treatment of cardiovascular diseases.