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目前,已证明诱导型一氧化氮合酶(iNOS)可通过增加一氧化氮(NO)生成促进急性肺损伤的发展,并延缓注射细菌脂多糖(LPS)动物低血压的发生。而最近研究表明,内皮素(ET)在败血症引起的急性肺损伤及血管衰蝎中起重要作用。但ET在其中的作用机制尚不明确。本实验作者通过观测特异性内皮素A受体(ET-AR)阻断剂P1/f1(一种22氨基酸肽)对注射LPS大鼠的平均动脉压、肺NO生成、肺湿/干比值、血清硝酸盐-亚硝酸盐(NO_3~--NO_2~-)水平、肺iNOS活性、肺iNOS蛋白表达的影响,以探讨ET是否是通过诱导iNOS表达促进NO生成,从而加剧LPS引发的急性肺损伤和低血压的。 方法 将体重250～350克的雄性SD大鼠根据注射的试剂不同分为四组:生理盐水(saline)组,LPS组,saline+P1/f1组和LPS+P1/f1组。其中,P1/f1在saline或LPS注射前15分钟给予。实验开始后,持续5小时动态观测四组动物的平均动脉压、呼出气中NO浓度、血清NO_3~--NO_2~-浓度。实验结束时,分别测定四组动物的血浆ET-1浓度、肺湿/干
At present, it has been demonstrated that inducible nitric oxide synthase (iNOS) promotes the development of acute lung injury by increasing nitric oxide (NO) production and delays the hypotensive effect of injecting bacterial lipopolysaccharide (LPS). Recent studies have shown that endothelin (ET) plays an important role in acute lung injury caused by sepsis and vascular failure. But the mechanism of ET in it is not clear yet. In this study, we observed the effects of specific endothelin A receptor (ET-AR) inhibitor P1 / f1 (a 22 amino acid peptide) on mean arterial pressure, lung NO production, Nitric oxide (NO_3 ~ - NO_2 ~ -), lung iNOS activity and lung iNOS protein expression in order to explore whether ET can promote NO production by inducing iNOS expression, and thus aggravate LPS-induced acute lung injury And low blood pressure. Methods Male Sprague-Dawley rats weighing 250-350 g were divided into four groups according to the injected agents: saline group, LPS group, saline + P1 / f1 group and LPS + P1 / f1 group. Of these, P1 / f1 was given 15 minutes prior to saline or LPS injection. After the start of the experiment, the average arterial pressure, the NO concentration in exhaled air and the NO 3 - - NO 2 - concentration in serum were observed dynamically for 5 hours. At the end of the experiment, plasma concentrations of ET-1 and wet / dry lungs were measured in four groups of animals