ABSTRACT
Objective:To investigate the correlation between serum levels of heme oxygenase-1 (HO-1) and lipoxin A4 (LXA4) and diabetic nephropathy, and to analyze the value of HO-1 and LXA4 in the diagnosis of diabetic nephropathy.Methods:A prospective cohort study was conducted in 185 patients with type 2 diabetes admitted to the Department of Endocrinology, Yan'an Hospital Affiliated to Kunming Medical University from January 2016 to January 2020. There were 96 cases with diabetic nephropathy (nephropathy group) and 89 cases without diabetic nephropathy (non nephropathy group). According to the stage of chronic kidney disease,the nephrotic group was divided into three subgroups: stage 1-2 group (31 cases), stage 3-4 group (40 cases) and stage 5 group (25 cases). Another 82 healthy volunteers were selected as the control group.Serum HO-1, LXA4, oxidative stress,inflammatory factors, glucose metabolism and renal function were detected. Pearson analysis of HO-1, LXA4 and oxidative stress, inflammatory factors, glucose metabolism and renal function index correlation, binary logistic regression analysis of diabetic nephropathy factors.Results:The serum HO-1 ((0.60 ± 0.20) μg/L) and LXA4 levels ((435.12 ± 22.42) ng/L) in nephrotic group were lower than those in non nephrotic ((0.72 ± 0.23) μg/L, (498.21 ± 29.48) ng/L)( t=29.351, 24.135, all P<0.05). The serum HO-1 and LXA4 levels in the 5 stage group were lower than those in the 3-4 stage and 1-2 stage group (all P<0.05). The serum HO-1 and LXA4 levels in the 3-4 stage group were lower than those in the 1-2 stage group (all P<0.05). Pearson correlation analysis showed that HO-1 was positively correlated with total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and estimated glomerular filtration rate (EGFR) ( r=0.516, 0.602, 0.617; all P<0.05), and was positively correlated with malondialdehyde (MDA) and homeostasis model insulin resistance (homeostasis model insulin resistance) Model assessment insulin resistance (HOMA-IR), urinary albumin creatinine ratio (UACR) LXA4 was negatively correlated with T-AOC, SOD and EGFR ( r=-0.559, 0.597, 0.637; all P<0.05), and positively correlated with MDA, IL-6, TGF-β1, HOMA-IR and UACR There was a negative correlation ( r=-0.498, -0.623, -0.725; all P<0.05). Binary logistic regression analysis showed that malondialdehyde ( OR=1.587, 95% CI 1.402-1.603, P=0.016), TGF-β1 ( OR=1.679, 95% CI 1.642-1.739, P=0.012), HOMA-IR ( OR=1.699、95% CI 1.534-1.739, P=0.009) were risk factors of diabetic nephropathy (all P<0.05). HO-1 ( OR=0.506, 95% CI 0.423-0.653, P<0.001) and LXA4 ( OR=0.492, 95% CI 0.409-0.535, P<0.001) were protective factors for DN ( P<0.001). After adjusting for MDA, TGF-β1 and HOMA-IR, HO-1 ( OR=0.485, 95% CI:0.402-0.564, P<0.001) and LXA4 ( OR=0.416, 95% CI:0.386-0.475, P<0.001) were still associated with DN. ROC analysis showed that the area under curve (AUC) of HO-1 and LXA4 were 0.820 (95% CI:0.760-0.880, P<0.001) and 0.763 (95% CI:0.691-0.836, P<0.001), respectively. The sensitivity and specificity were 71.88%, 80.90%, 75.00% and 84.27%, respectively. Conclusion:The decrease of serum LXA4 and HO-1 levels is closely related to diabetic nephropathy, which can be used as a biological indicator for the diagnosis of diabetic nephropathy.