卡托普利对光气所致大鼠急性肺损伤的改善作用及其机制

doi:10.3969/j.issn.1004-616x.2026.02.002

Abstract

Abstract: OBJECTIVE: To establish a phosgene-induced acute lung injury（ALI） model in SD rats and to investigate mechanisms for improvement effect of captopril on ALI rats. METHODS: Forty male SD rats were randomly divided into control,phosgene poisoning（Phos）,Captopril（CAP） and combined groups with phosgene and captopril（Phos+CAP）, with ten rats in each group. Rats dynamically inhaled 41 mg/m³ phosgene for 30 minutes in Phos and Phos+CAP groups and received intraperitoneal injection with 5 mg/kg Captopril immediately after phosgene poisoning in CAP and Phos+CAP groups. Survival rates of the rats were determined within 24 hours after administration. Lung function of the rats was measured using a whole-body plethysmography（WBP）system after 24 hours. Rat lung tissues were collected to measure the lung coefficient. HE staining of lung tissues was performed to assess pathological damage. Total protein concentration was determined in bronchoalveolar lavage fluid（BALF） by BCA method. Inflammatory factors including IL-1β and TNF-α were detected by ELISA in serum, BALF and lung homogenate. Activities of superoxide dismutase（SOD） and glutathione peroxidase（GPx）,content of malondialdehyde（MDA） were measured by kits. Levels of Angiotensin-converting enzyme（ACE）and angiotensin Ⅱ（Ang Ⅱ） were determined by immunohistochemistry and ELISA. Apoptosis in lung tissues was observed by TUNEL staining. Expression of Bcl-2 in lung tissue was detected by Western blotting. RESULTS: Compared with the control group, the 24 h survival rate of rats in the phosgene exposure group was 80%.Pulmonary hemorrhage spots were observed,and HE staining showed typical pathological changes of acute lung injury. Levels of IL-1β and TNF-α in bronchoalveolar lavage fluid,lung homogenate,and serum were elevated（P<0.01）. Activities of SOD and GPx were decreased（P<0.05）,while MDA content as well as ACE and Ang Ⅱ levels were significantly increased（P<0.01）. Apoptotic cell density was markedly increased（P < 0.01） along with reduced expression of Bcl-2 protein（P<0.01）. Compared with Phos group,levels of IL-1β and TNF-α and the activity of angiotensin-converting enzyme（ACE） and content of angiotensin Ⅱ（Ang Ⅱ） were significantly decreased in the Phos+CAP group（P<0.05）. The number of apoptotic cells decreased（P<0.05）,and Bcl-2 protein expression declined（P<0.01）. CONCLUSION: Captopril significantly alleviated acute lung injury which was induced by phosgene. Alleviation mechanisms may be related to alveolar barrier repair, enhanced antioxidant defense and inflammation suppression. This study provides experimental evidence for a clinical approach of phosgene poisoning.

Key words: captopril, phosgene, acute lung injury, inflammation, oxidative stress

CLC Number:

WANG Changyan, LI Jiawei, WANG Hui, CHEN Jinhe, FAN Zhenpeng, SHI Minjie, LI Wenli, ZHANG Rongqiang. Improvement effect of captopril on phosgene-induced acute lung injury in rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(2): 93-101.

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Improvement effect of captopril on phosgene-induced acute lung injury in rats

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