Mechanism of Lung Tissue and Endothelial Injury and the Effect of L-arginine in Rats with Chronic Intermittent Hypoxia

ZHENG Shuguang; GUO Xiangxiang; GAO Li; WANG Li

doi:10.12102/j.issn.1672-1349.2025.20.006

Abstract：Objective:To study the effect of chronic intermittent hypoxia(CIH)on endothelial dysfunction and the protective effect of L-arginine on endothelial function.Methods:Thirty SD rats were randomly divided into control group(12 rats)and CIH group(18 rats).The CIH group was placed in an intermittent hypoxic chamber for 8 hours per day for 6 weeks.The control group was placed in a normal oxygen chamber(21%).After 6 weeks,6 rats in each group were randomly selected to collect blood and lung tissue samples.Serum 3-nitrotyrosine(3-NT)content was determined by enzyme-linked immunosorbent assay,and nitric oxide(NO)content in peripheral blood and lung tissue was determined by nitric reductase assay.The contents of malondialdehyde(MDA)and superoxide anion(O2-),as well as the activities of superoxide dismutase(SOD),endothelial nitric oxide synthase(eNOS),and inducible nitric oxide synthase(iNOS)in lung tissue,were determined by colorimetry.The lung tissues from two groups of rats were collected for pathological sectioning and examined under a microscope following hematoxylin-eosin(HE)staining.The remaining 6 rats in the control group were still set as the control group,and the remaining 12 rats in the CIH group were randomly divided into the L-arginine group and the model group,with 6 rats in each group.The L-arginine group was intraperitoneally injected with L-arginine(500 mg/kg),while the other two groups were administered the same volume of normal saline.After observation for 1 hour,the rats were anesthetized,and the indexes in experiment 1 were monitored again.Results:Results of experiment 1,serum NO content in CIH group was significantly lower than that in control group.Serum 3-NT in CIH group was significantly higher than that in control group.There was no significant difference in eNOS protein expression between CIH group and control group,but eNOS activity in CIH group was significantly lower than that in control group.The protein expression level and iNOS activity in CIH group were significantly higher than those in control group.The content of MDA and O2-in lung tissue of CIH group was higher than that of control group,while the activity of SOD was significantly lower than that of control group.In the control group,the lung tissue structure was clear and the pulmonary artery wall was thin.In the CIH group,inflammatory cell infiltration was evident in the pulmonary artery tissue,the pulmonary artery wall was generally thickened,the media was markedly thickened,thrombi of varying sizes were present in the lumen,the lumen was significantly narrowed,the number of cells in the transverse section of the pulmonary artery increased,and there was prominent pulmonary angiogenesis,endothelial cell injury,and detachment.Results of experiment 2,the serum NO content in the L-arginine group and the model group was higher than that in the control group,and the serum NO content in the L-arginine group was higher than that in the model group.The serum 3-NT level in the model group was higher than that in the control group,and the 3-NT content in the L-arginine group was lower than that in the model group.The eNOS protein expression level and eNOS activity in lung tissues of the L-arginine group and the model group were higher than those of the control group,and those of the L-arginine group were higher than those of the model group.The expression level of iNOS protein and the activity of iNOS in the lung tissues of the L-arginine group and the model group decreased,and those of the L-arginine group were lower than those of the model group.The content of MDA and O2-in the lung tissues of the L-arginine group and the model group was higher than that of the control group,and that of the model group was higher than that of the L-arginine group.The activity of SOD in the lung tissues of the model group was significantly lower than that of the control group,and the activity of SOD in the L-arginine group was higher than that of the model group.After L-arginine treatment,inflammatory cell infiltration and endothelial cell damage reduced in lung tissue,but there were still thrombi in pulmonary arterioles,wall thickening,and lumen stenosis,and pulmonary angiogenesis was not alleviated.Conclusion:L-arginine can increase the NO content in endothelial cells by enhancing iNOS and SOD activity and decreasing MDA content,thus playing some role in protecting endothelial cells and providing new therapeutic target for the clinical treatment of OSAHS.At the same time,pathological results also confirm that L-arginine can reduce the inflammatory response in lung tissue,but there was no significant improvement in pulmonary thrombosis or pulmonary vascular remodeling.