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【正文】 水楊酸 水楊酸鈉 乙酰水楊酸 繡線菊 冬青油 亞瑟 艾興格林 （ Arthur Eichengr252。n 1867 1949） 費(fèi)里克斯 霍夫曼 (1868 –1946) 海因里希 德萊塞 1853年法國(guó)化學(xué)家 Charles Frederic Gerhardt 止痛、鎮(zhèn)咳 海洛因 (Heroin德文 heroisch) Felix Hoffman Indices of biosynthesis and the capacity to form prostacyclin (PGI2) and thromboxane (TxA2). The primary bioactive products, TxA2 and PGI2, rapidly degrade into the inactive hydrolysis products, TxB2 and 6ketoPGF1α. Measurements of these latter products are poor indices of the biosynthesis of prostaglandins because they are confounded by ex vivo formation of the parent pounds in blood and other biological samples. They are, however, useful markers of the capacity of a tissue to generate the parent pound, for example, measurements of serum TxB2 as an index of cyclooxygenase activity in platelets. These products are enzymatically metabolized further in a tissuespecific manner to products that are excreted in urine. Measurements of these chemically stable products reflect in vivo formation of the parent pounds. 前列腺素生物合成和代謝途徑 前列腺素 ( prostag land ins) 人體中分布最廣、效應(yīng)最大的生物活性物質(zhì)之一 , 控制血管收縮、調(diào)節(jié)血壓、傳遞痛覺(jué)、調(diào)節(jié)炎癥等。 使體溫升高 (發(fā)燒 )及促進(jìn)炎癥 (產(chǎn)生疼痛 )。 凝血 噁 烷 ( thromboxane) 前列腺素 環(huán)加氧酶 ( cyc looxygenase, COX ) 花生四烯酸 Aspirin inhibits platelet cyclooxygenase (COX)1. Aspirin irreversibly acetylates Ser529 in the human COX1, converting to salicylic acid, a weak reversible COX inhibitor. Covalent modification of platelet COX1 disrupts biotransformation of arachidonic acid to prostaglandin G2 (PGG2), and subsequently to TxA2, for the lifetime of that platelet. 花生四烯酸 Aspirin 作用機(jī)制示意圖 John Vane, 1982年諾貝爾生理學(xué)和醫(yī)學(xué)獎(jiǎng) Nonsteroidal antiinflammatory drug (NSAID) interaction to undermine the antiplatelet effect of aspirin. Cyclooxygenase (COX) enzymes exist as dimers and the substrate arachidonic acid gains access to the catalytic site of 1 monomer via a hydrophobic channel, whereas the second monomer stabilizes the protein to facilitate the interaction. Acetylation of its target serine residue obstructs access of arachidonic acid (AA) to the catalytic site, blocking thromboxane A2 (TxA2) formation irreversibly in the case of platelet COX1. Nonspecific traditional NSAIDs, such as ibuprofen, block COX1 reversibly as petitive active site inhibitors and, if in previous occupancy of the active site, block access of aspirin to its target serine. Functionally, this would replace sustained maximal suppression of platelet TxA2 throughout a typical dosing interval with transient maximal inhibition sufficient for platelet inhibition for a fraction of the dosing interval. Reproduced with permission from CatellaLawson et 花生四烯酸 Aspirin 作用機(jī)制示意圖 Cyclooxygenase (COX) COX1 COX2 COX3 Chemical structures of NSAIDs and related pounds COX 抑制劑和非甾體抗炎藥 Chemical structures of NSAIDs and related pounds 例三：硫酸軟骨素分子探針 與 神經(jīng)元 再生研究 克利斯多夫 里夫 第一代超人飾演者 墜馬意外導(dǎo)致脊髓損傷 造成頸部以下 終身癱瘓 最終只能憑借呼吸機(jī)維持生命 桑蘭 跳馬比賽意外導(dǎo)致下肢終身癱瘓 神經(jīng)元受到損傷后自身修復(fù)微乎其微，機(jī)體也無(wú)法分裂出新的神經(jīng)細(xì)胞。導(dǎo)致脊髓一旦受到嚴(yán)重?fù)p傷，便可能引起終身癱瘓的可怕后果。 研究受傷神經(jīng)元為何無(wú)法再生的原因，從而研究小分子藥物迫在眉睫！ ― Drugs to protect vulnerable neurons and encourage neural circuits to reform could one day improve the outlook for patients with acute spinal cord trauma.‖ Nature 2022, 503, S10 CSPG的釋放與神經(jīng)元的再生抑制 I 正常神經(jīng)細(xì)胞 III 受損神經(jīng)細(xì)胞 IV 膠質(zhì)淤痕，生長(zhǎng)抑制 細(xì)胞死亡 II 外傷導(dǎo)致脊髓損傷 CSPG = Chondroitin
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