一氧化氮治疗急性呼吸窘迫综合征的临床进展

Clinical progress of nitric oxide for treating acute respiratory distress sysdrome

急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是在严重感染、休克、创伤及烧伤等非心源性疾病过程中,肺毛细血管内皮细胞和肺泡上皮细胞损伤造成弥散性肺间质及肺泡水肿,导致的急性低氧性呼吸功能不全或衰竭。目前对于ARDS的治疗手段众多,其中之一的选择性肺血管扩张剂一氧化氮(NO)于20世纪后期开始进入临床治疗领域。NO是一种非胆碱能、非肾上腺素能神经递质,参与痛觉传入的感觉传递过程。其广泛分布于生物体内各组织中,对心脑血管、神经、免疫调节等方面有着十分重要的生物学作用。NO是一种生物信使分子,极不稳定,分子小,结构简单,常温下为气体,微溶于水,具有脂溶性,可快速透过生物膜扩散,生物半衰期只有3～5秒,其生成依赖于一氧化氮合成酶(NOS)。Palmer等证明了NO是通过血管内皮细胞中的L-精氨酸-NO合成途径产生的,NO进入血管平滑肌细胞之后,通过激活鸟苷酸环化酶(GC),增加细胞内cGMP的含量,从而激活依赖于cGMP的蛋白激酶,促使肌球蛋白轻链去磷酸化而松弛血管平滑肌,达到扩张血管的作用。

Acute respiratory distress syndrome（ARDS） is a clinical syndrome occurring after serious infection,trauma,shock and other non-cardiac diseases attacks.Pulmonary capillary endothelial cells and alveolar epithelial cells are damaged,causing the diffuse interstitial and alveolar pulmonary edema,leading to acute hypoxia respiratory insufficiency or failure.There are many treatments for ARDS,such as the nitric oxide（NO）,one of the selective pulmonary vasodilators,which was applied into the field of clinical treatment in the late 20th century.NO is a non-cholinergic and non-adrenergic neurotransmitter and has an act in the process of pain transfer.It is widely distributed in various tissues in vivo and has a very important biological role in the cardiovascular system,nerves system and immune regulation.NO is a biological messenger molecule,and has features of being extremely unstable,little molecular weight and simple structure.It can spread rapidly through the membrane,which depends on the generation of nitric oxide synthase（NOS）.Palmer et al.proved that NO generated through the pathway of L-arginine-NO in endothelial cells and dispersed from the endothelial cells to vascular smooth muscle cells,in which it activated guanylate cyclase（GC） to increase the intracellular cGMP levels,thereby activating cGMP-depending protein kinase,and promoting myosin light chain dephosphorylation and relaxing vascular smooth muscle,dilating blood vessels.