Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.