Guzel Ahmet, Basaran Umit Nusret, Aksu Burhan, Kanter Mehmet, Yalcin Omer, Aktas Cevat, Guzel Aygul, Karasalihoglu Serap
Trakya University Faculty of Medicine, Department of Pediatrics, 22030 Edirne, Turkey.
Int J Pediatr Otorhinolaryngol. 2008 Aug;72(8):1241-50. doi: 10.1016/j.ijporl.2008.05.001. Epub 2008 Jun 24.
The aim of this study was to evaluate the efficiency of inducible nitric oxide synthase (iNOS) specific inhibitor, S-methylisothiourea sulfate (SMT) in preventing lung injury after different pulmonary aspiration materials in rats.
The experiments were performed in 80 Sprague-Dawley rats, ranging in weight from 220 to 250 g, randomly allotted into one of the eight groups (n=10): normal saline (NS, control), Biosorb Energy Plus (BIO), sucralfate (SUC), hydrochloric acid (HCl), NS+SMT treated, BIO+SMT treated, SUC+SMT treated, and HCl+SMT treated. NS, BIO, SUC, HCl were injected in to the lungs in a volume of 2 ml/kg. The rats received twice daily intraperitoneal injections of 20 mg(kg day) SMT (Sigma Chemical Co.) for 7 days. Seven days later, rats were killed, and both lungs in all groups were examined immunohistochemically and histopathologically.
Our data show that SMT inhibits the inflammatory response significantly reducing (p<0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Furthermore, our data suggest that there is a significant reduction in the activity of iNOS and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with SMT therapy.
It was concluded that SMT treatment might be beneficial in lung injury, therefore shows potential for clinical use.
本研究旨在评估诱导型一氧化氮合酶(iNOS)特异性抑制剂硫酸S-甲基异硫脲(SMT)在预防大鼠不同肺吸入物质后肺损伤方面的效果。
实验选用80只体重在220至250克之间的Sprague-Dawley大鼠,随机分为八组之一(n = 10):生理盐水(NS,对照组)、生物吸附能量增强剂(BIO)、硫糖铝(SUC)、盐酸(HCl)、NS + SMT处理组、BIO + SMT处理组、SUC + SMT处理组和HCl + SMT处理组。将NS、BIO、SUC、HCl以2毫升/千克的体积注入肺内。大鼠每天接受两次腹腔注射20毫克/(千克·天)的SMT(Sigma化学公司),共7天。7天后,处死大鼠,对所有组的双肺进行免疫组织化学和组织病理学检查。
我们的数据表明,SMT可抑制炎症反应,在不同的肺吸入模型中显著减少(p < 0.05)支气管周围炎性细胞浸润、肺泡间隔浸润、肺泡水肿、肺泡渗出物、肺泡组织细胞、间质纤维化、肉芽肿和坏死形成。此外,我们的数据表明,在不同的肺吸入模型中,经SMT治疗后肺组织中iNOS的活性显著降低,表面活性蛋白D的表达增加。
得出的结论是,SMT治疗可能对肺损伤有益,因此具有临床应用潜力。