細胞因子在急性肺損傷_急性呼吸窘迫綜合征中的作用

1、細胞因子在急性肺損傷_急性呼吸窘迫綜合征中的作用         細胞因子之間存在復(fù)雜的相互作用,如促炎因子TNF-可刺激IL-4、IL-10等抗炎因子的分泌,而后者被激活后又可強力抑制TNF-、IL-1、IL-6等促炎因子的合成,相互作用。近年的研究證實,在ALI/ARDS患者中可檢測到多種細胞因子,例如ARDS患者肺泡強灌洗液中前炎性因子(TNF、IL-1、INF-、IL-6)和抗炎因子( IL-4、IL-10、IL-13、IL-1ra等)均明顯升高。代寫職稱論文在兔ALI模型中, TNF-首先增高,于0. 5

2、h達到高峰,隨后IL-1和IL-8增高,并于2h達高峰,也因此認為TNF-是啟動因子20。另有研究發(fā)現(xiàn),ARDS患者血漿IL-1升高21。ALI患者血漿IL-6、IL-8、IL-10,水平升高,而且IL-6、IL-8血漿水平與ALI的發(fā)病率和病死率密切相關(guān)。ALI/ARDS患者前3d IL-6、IL-8、TNF受體、肺表面活性相關(guān)蛋白D產(chǎn)生過多提示臨床預(yù)后不佳22。研究也證明,促炎介質(zhì)和抗炎介質(zhì)的不平衡是加重炎性反應(yīng),促進ALI/ARDS發(fā)生發(fā)展的重要因素。在ALI/ARDS中促炎因子和抗炎因子均增高,但抗炎因子相對濃度低,且時間滯后。研究發(fā)現(xiàn), ALI大鼠肺組織中TNF-mRNA表達2h達高

3、峰,隨后迅速下降;IL-1mRNA表達2h顯著增高, 6h達高峰,隨后迅速下降; IL-1ramRNA表達晚于前者, 6h開始升高且為峰值, 24h仍高于對照組23。表明在ALI時,TNF-及IL-1mRNA表達明顯早于IL-1ramRNA,提示ALI早期存在炎性介質(zhì)/抗炎介質(zhì)失衡。國外研究發(fā)現(xiàn),有ARDS危險患者第1d和第3d支氣管肺泡灌洗液中IL-10濃度偏低,但ARDS患者第1d和第3d支氣管肺泡灌洗液中IL-10濃度顯著升高,而持續(xù)ARDS患者的支氣管肺泡灌洗液中IL-10濃度在21d幾乎測不到24。同時,在ARDS開始期支氣管肺泡灌洗液中TNF-/IL-10比值減小,而在ARDS進展

4、期上升。 5展望通過對ALI/ARDS相關(guān)細胞因子的研究發(fā)現(xiàn),代寫工作總結(jié)促炎和抗炎細胞因子的失衡是關(guān)鍵,因此重建細胞因子的平衡有望成為治療ALI/ARDS的突破點,通過補充外源性抗炎因子,抑制炎性細胞因子的產(chǎn)生,以及補充促炎細胞因子特異性抗體等,在阻止ALI/ARDS的發(fā)生、發(fā)展中是至關(guān)重要的。但目前關(guān)于細胞因子的研究和針對性治療大多局限于動物試驗階段取得很大成功,應(yīng)用到臨床后并未取得預(yù)期的療效。分析主要原因是由于細胞因子種類及其數(shù)量繁多,且相互作用形成了一個級聯(lián)的網(wǎng)絡(luò)系統(tǒng),單單針對幾種細胞因子治療難以阻斷ALI/ARDS的進一步發(fā)展。因此,需要對細胞因子及其網(wǎng)絡(luò)信號機制進行深入研

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