代写论文 >> 医学论文 >> 细胞因子在急性肺损伤_急性呼吸窘迫综合征中的作用
细胞因子在急性肺损伤_急性呼吸窘迫综合征中的作用
- 作者:admin 来源:网络 日期:2008-6-7 21:39:05
细胞因子之间存在复杂的相互作用,如促炎因子TNF-α可刺激IL-4、IL-10等抗炎因子的分泌,而后者被激活后又可强力抑制TNF-α、IL-1、IL-6等促炎因子的合成,相互作用。
近年的研究证实,在ALI/ARDS患者中可检测到多种细胞因子,例如ARDS患者肺泡强灌洗液中前炎性因子(TNF、IL-1、INF-γ、IL-6)和抗炎因子( IL-4、IL-10、IL-13、IL-1ra等)均明显升高。代写职称论文在兔ALI模型中, TNF-α首先增高,于0. 5h达到高峰,随后IL-1β和IL-8增高,并于2h达高峰,也因此认为TNF-α是启动因子[20]。另有研究发现,ARDS患者血浆IL-1升高[21]。ALI患者血浆IL-6、IL-8、IL-10,水平升高,而且IL-6、IL-8血浆水平与ALI的发病率和病死率密切相关。
ALI/ARDS患者前3d IL-6、IL-8、TNF受体、肺表面活性相关蛋白D产生过多提示临床预后不佳[22]。研究也证明,促炎介质和抗炎介质的不平衡是加重炎性反应,促进ALI/ARDS发生发展的重要因素。在ALI/ARDS中促炎因子和抗炎因子均增高,但抗炎因子相对浓度低,且时间滞后。研究发现, ALI大鼠肺组织中TNF-αmRNA表达2h达高峰,随后迅速下降;IL-1βmRNA表达2h显著增高, 6h达高峰,随后迅速下降; IL-1ramRNA表达晚于前者, 6h开始升高且为峰值, 24h仍高于对照组[23]。表明在ALI时,TNF-α及IL-1βmRNA表达明显早于IL-1ramRNA,提示ALI早期存在炎性介质/抗炎介质失衡。国外研究发现,有ARDS危险患者第1d和第3d支气管肺泡灌洗液中IL-10浓度偏低,但ARDS患者第1d和第3d支气管肺泡灌洗液中IL-10浓度显著升高,而持续ARDS患者的支气管肺泡灌洗液中IL-10浓度在21d几乎测不到[24]。同时,在ARDS开始期支气管肺泡灌洗液中TNF-α/IL-10比值减小,而在ARDS进展期上升。
5 展 望
通过对ALI/ARDS相关细胞因子的研究发现,代写工作总结促炎和抗炎细胞因子的失衡是关键,因此重建细胞因子的平衡有望成为治疗ALI/ARDS的突破点,通过补充外源性抗炎因子,抑制炎性细胞因子的产生,以及补充促炎细胞因子特异性抗体等,在阻止ALI/ARDS的发生、发展中是至关重要的。但目前关于细胞因子的研究和针对性治疗大多局限于动物试验阶段取得很大成功,应用到临床后并未取得预期的疗效。分析主要原因是由于细胞因子种类及其数量繁多,且相互作用形成了一个级联的网络系统,单单针对几种细胞因子治疗难以阻断ALI/ARDS的进一步发展。因此,需要对细胞因子及其网络信号机制进行深入研究,争取在ALI/ARDS治疗上取得突破。
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