當(dāng)前位置：首頁 > 新聞動態(tài) > 行業(yè)新聞新冠肺炎“炎癥風(fēng)暴”是近期公眾關(guān)注的諸多熱點話題之一；所謂“炎癥風(fēng)暴”即全身炎癥反應(yīng)綜合征（SIRS），人體的炎癥因子，不僅可以殺掉病毒，也會給自身造成損害，某些新冠患者后期可能突然啟動了一個“炎癥風(fēng)暴”，結(jié)果導(dǎo)致各個器官的功能衰竭。那么應(yīng)該如何應(yīng)對“炎癥風(fēng)暴”呢？中南大學(xué)湘雅醫(yī)學(xué)院林韶輝博士撰文“有效針對新冠肺炎的“炎癥風(fēng)暴”——Omega-3多不飽和脂肪酸”，表達了自己的一些觀點，或許會給大家一些思考和啟發(fā)。
一、新冠肺炎專家說
1. 武漢金銀潭醫(yī)院：上海中山醫(yī)院重癥醫(yī)學(xué)科副主任鐘鳴醫(yī)生（2020年1月24到達武漢），2020年2月3日，南方人物周刊對鐘醫(yī)生進行獨家專訪，提到救治初期，所面臨的困難之中，有的新冠患者后期可能突然啟動了一個“炎癥風(fēng)暴”，這種炎癥風(fēng)暴導(dǎo)致了各個器官的功能衰竭，一旦進入這個狀態(tài)，我們的治療很難把它拉回來。
2. 武漢大學(xué)中南醫(yī)院：《美國醫(yī)學(xué)會雜志》2月7日在線發(fā)布了武漢大學(xué)中南醫(yī)院重癥監(jiān)護室（ICU）主任彭志勇博士領(lǐng)銜的一項回顧性分析，研究團隊認為，新冠肺炎致死的三大主要機制：
中性粒細胞增多，與細胞因子風(fēng)暴有關(guān)；
D-二聚體升高反映凝血激活，提示持續(xù)的炎癥反應(yīng)；
血尿素升高提示急性腎損傷，這是感染、休克和缺氧的綜合結(jié)果。
3. 種種跡象表明，這些重癥患者中發(fā)生了不可逆轉(zhuǎn)的“炎癥風(fēng)暴”。而一旦患者發(fā)生“炎癥風(fēng)暴”，糖皮質(zhì)激素是對抗炎癥風(fēng)暴的武器之一，可以給免疫系統(tǒng)“滅火”，減輕機體損傷。不過，糖皮質(zhì)激素是一把“雙刃劍”。一方面它可以減輕炎癥反應(yīng)，有利于改善缺氧、呼吸窘迫癥狀；但長期大劑量使用也可能引發(fā)諸多不良反應(yīng)。不少經(jīng)過大劑量激素治療的“非典”患者，都留下了如股骨頭壞死等嚴重后遺癥。
二、“炎癥風(fēng)暴”與Omega-3多不飽和脂肪酸
3. Omega-3 PUFA對抗炎癥反應(yīng)的作用機制
圖1. 長鏈不飽和脂肪酸代謝示意圖
4. 多種文獻證明，為了減少患者還可能發(fā)生爆發(fā)性炎癥反應(yīng)，使用高純度的 Omega-3 PUFA制劑，可以減低炎癥風(fēng)暴的發(fā)生風(fēng)險。具體表現(xiàn)
4.1 Omega-3 PUFA富集于細胞膜，參與炎癥反應(yīng)調(diào)控過程，減少炎性細胞產(chǎn)生促炎性細胞因子；
Omega-3 PUFA富集于細胞膜，提高細胞膜EPA和DHA脂肪酸的比例[11, 12]，影響胞內(nèi)信號傳導(dǎo)，抑制炎癥相關(guān)的轉(zhuǎn)錄因子NF-kappa B的轉(zhuǎn)錄活性[13, 14]，從而減少促炎性細胞因子TNF-alpha、IL-6 和IL-8等的表達[15]。
花生四烯酸類脂質(zhì)經(jīng)一系列酶催化產(chǎn)生促炎癥調(diào)節(jié)作用的前列腺素（PGE2）和白三烯B4等。這些促炎性介質(zhì)進而可激活中性粒細胞、巨噬細胞，刺激炎癥細胞因子TNF-α、IL-1、IL-2、IL-8和干擾素（Interferon, IFN）等釋放增多。Omega-3和Omega-6兩類 PUFA競爭相同的脂肪酸代謝酶（Elovl5和FADS2）系統(tǒng)[16-18]，從而干擾促炎性介質(zhì)的生成。
EPA和DHA經(jīng)代謝產(chǎn)生消散素（Resolvins）和保護素（Protections）。實驗研究證實，消散素和保護素在關(guān)節(jié)炎[19]、結(jié)腸炎[20]、哮喘[21, 22]等多種炎性疾病中發(fā)揮重要的抗炎作用[23, 24] 。例如，resolvin E1，resolvin D1和protectin D1能抑制浸潤性中性粒細胞的細胞遷移，從而減輕局部炎癥[24]。此外，resolvin D1和protectin D1還能抑制TNF-α and IL-1β的產(chǎn)生，從而減弱炎癥反應(yīng)[25, 26]。
5. Omega-3 PUFA緩解炎癥的具體臨床獲益
5.1 C反應(yīng)蛋白等炎癥指標(biāo)顯著下降，血紅蛋白和白細胞、血小板等細胞類群總量顯著上升。
表1. ICU患者使用Omega-3 PUFA帶來的生理指標(biāo)和臨床指標(biāo)獲益
5.2 敗血癥狀明顯下降，治療用抗生素使用時間縮短，全身炎癥反應(yīng)綜合征減少，器官功能障礙后遺癥發(fā)生率減少，死亡率下降；
美國田納西大學(xué)附屬醫(yī)院和西班牙多所醫(yī)院的臨床研究表明，對于重癥創(chuàng)傷患者和膿毒癥患者等ICU患者，每天1~3克Omega-3 PUFA營養(yǎng)液可以有效降低菌血癥、敗血癥并發(fā)癥發(fā)生（下降14%[29]~35%[30]），明顯降低治療用抗生素使用時間和腹腔內(nèi)膿腫發(fā)生率[30]。而使用更高Omega-3 PUFA含量（4克以上）的營養(yǎng)液后，創(chuàng)傷病人全身炎癥反應(yīng)綜合征發(fā)生人數(shù)顯著下降[27]；膿毒癥、敗血癥患者的器官功能障礙發(fā)生率減少達到43%[31]，死亡率顯著下降13.1%[29]~19.4%[31]。
表2. 創(chuàng)傷患者和敗血癥患者使用Omega-3 PUFA的臨床獲益
5.3 改善氧合狀態(tài)，減少呼吸機使用，縮短ICU監(jiān)護時間；
6.2 生物利用度高，保證體內(nèi)有效富集。
6.3 添加中鏈甘油三酯（MCTs），促進Omega-3 PUFA快速細胞富集，為重癥患者的癥狀緩解贏得時間。添加MCT的Omega-3脂肪乳的體內(nèi)富集時間更短（術(shù)后第六天即檢測到病患血清磷脂和紅細胞細胞膜中的EPA和DHA顯著升高）[35]，激發(fā)免疫更強（第六天起外周血細胞釋放的白三烯B5含量已增長約2倍）[36]；
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