Ghazi-Khansari Mahmoud, Mohammadi-Karakani Ali, Sotoudeh Masoud, Mokhtary Parvin, Pour-Esmaeil Ebraheim, Maghsoud Shirin
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Appl Toxicol. 2007 Jul-Aug;27(4):342-9. doi: 10.1002/jat.1212.
Although different treatment modalities have been implemented for pulmonary fibrosis, the results have not been promising and these conditions have been considered untreatable and irreversible. Thus, a plethora of new drugs has been tried for the control of this condition in recent years. This study examined the effects of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on paraquat-induced pulmonary fibrosis in rats, through biochemical and histopathological parameters. Male albino Wistar rats were divided into eight groups (n = 4-5 each), including control, paraquat, captopril alone, captopril treatment and pre-treatment, enalapril alone, enalapril treatment and pre-treatment. After 21 days of treatment, the lungs were removed and the levels of hydroxyproline, glutathione and lipid peroxidation were determined. Angiotensin-converting enzyme inhibitors showed no effect on glutathione and lipid peroxidation. The results also demonstrated that captopril and enalapril improved pulmonary fibrosis as shown by histopathology, as well as a decreased content of hydroxyproline (P < 0.001) in the lung tissue. In conclusion, the present findings suggest that the antifibrotic effect of these drugs may be related to the inhibition of angiotensin-converting enzyme.
尽管针对肺纤维化已经实施了不同的治疗方式,但结果并不理想,这些病症一直被认为是无法治疗且不可逆转的。因此,近年来已经尝试了大量新药来控制这种病症。本研究通过生化和组织病理学参数,研究了两种血管紧张素转换酶抑制剂卡托普利和依那普利对百草枯诱导的大鼠肺纤维化的影响。雄性白化Wistar大鼠被分为八组(每组n = 4 - 5),包括对照组、百草枯组、单独使用卡托普利组、卡托普利治疗及预处理组、单独使用依那普利组、依那普利治疗及预处理组。治疗21天后,取出肺脏并测定羟脯氨酸、谷胱甘肽和脂质过氧化水平。血管紧张素转换酶抑制剂对谷胱甘肽和脂质过氧化没有影响。结果还表明,卡托普利和依那普利通过组织病理学显示改善了肺纤维化,并且肺组织中羟脯氨酸含量降低(P < 0.001)。总之,目前的研究结果表明这些药物的抗纤维化作用可能与抑制血管紧张素转换酶有关。