Role of macrophage polarization in lung injury in obese rats with acute necrotizing pancreatitis

Abstract

Objective To investigate whether obesity aggravates acute lung injury and its mechanism in acute necrotizing pancreatitis. Methods Twenty-four male Sprague-Dawley rats were randomly divided into a normal diet control group (N-control), a normal diet-ANP group (N-ANP), and a high-fat diet control group (H-control), and a high fat diet-ANP group (H-ANP). Serum amylase (AMY), lipase (LIP), triglyceride (TG) and total cholesterol (TC) were determined by automatic biochemical analyzer. CD68, CD11c, CD206, toll like receptor-4 (TLR4), myeloperoxidase (MPO), interleukin (IL)-1β and nuclear factor-κB (NF-κB) in the lung tissue were detected by immunofluorescence or immunohistochemistry. The pancreas and lung tissues were observed under microscope and scored. SPSS 22.0 software was used. The data were expressed as mean±standard deviation. The t test, one-way ANOVA and SNK test were used. Results The TG and TC of the H-control group were (1.00±0.36) and (2.51±0.41) U/L, which were higher than those of the N-control group (0.53±0.19) and (1.72±0.52) U/L. The differences were statistically significant (t=-3.288, -3.062, P<0.05); AMY and LIP of the N-ANP group were (8 690.00±1 951.35), (9 650.00±1 810.19) U/L, which were higher than the N-control group (2 018.50±382.05), (90.26±7.00) U/L, the difference was statistically significant (q=9.452, 18.090, P<0.05); the LIP of the H-ANP group was (39 705.75±1 345.55) U/L, which was higher than the N-ANP group (q=59.940, P<0.05). The pancreas and lung scores in the N-ANP group were (11.40±1.80) and (6.62±1.06) points, which were higher than those in the N-control group (0.31±0.29) and (0.75±0.88). The difference was statistically significant (q=21.950, 17.160, P<0.05). The lung score of the H-ANP group was (8.19±1.07) points, which was higher than that of the N-ANP group (q=4.017, P<0.05), and the difference was statistically significant. The lung NF-κB of N-ANP group was (0.38±0.02), which was higher than that of N-control group (0.23±0.02) and lower than that of H-ANP group (0.48±0.01). The difference was statistically significant (q=21.830, 13.030, P<0.05). The number of IL-1β, MPO, CD68+ , CD68+ /CD11C+ , CD68+ /TLR4+ cells in the N-ANP group was (43.80±4.29), (105.81±5.37), (34.17±3.27), (13.32±1.83), (18.43±1.06), higher than the N-control group (4.93±1.13), (10.37±1.77), (20.16±2.42), (1.54±0.75), (8.37±1.40), the difference was statistically significant (q=29.530, 51.010, 15.261, 17.952, 20.965, P<0.05), lower than the H-ANP group (92.58±5.83), (175.71±8.85), (41.61±2.56), (16.92±1.96), (22.91±2.10), the difference was statistically significant (q=36.820, 37.100, 8.176, 8.079, 6.467, P<0.05). The number of lung CD68+ /CD206+ cells in the N-ANP group was (20.43±1.30), which was higher than that in the N-control group (11.65±1.51) and H-ANP group (14.83±1.83). The difference was statistically significant (q=16.613, 10.682, P<0.05). Conclusion Obesity can aggravate ALI in ANP, which may be related to the degree of activation of TLR4 signaling pathway in lung macrophages, leading to the polarization of macrophages to proinflammatory direction and release of more inflammatory mediators. Key words: Obesity; Acute necrotizing pancreatitis; Acute lung injury