Inhibitory effect of lidocaine on Kupffer cell inflammatory response and its effect on liver abscess formation in diabetic mice
10.3969/j.issn.1001-5256.2022.06.023
- VernacularTitle:利多卡因抑制糖尿病小鼠Kupffer细胞炎症反应及对肝脓肿形成的影响
- Author:
Ruibin WANG
1
;
Yuzheng LU
1
;
Jinglin ZHU
1
;
Wei WANG
1
;
Guang JIA
1
Author Information
1. Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Publication Type:Original Articles_Other Liver Diseases
- Keywords:
Diabetes Mellitus;
Liver Abscess;
Kupffer Cells;
Lidocaine
- From:
Journal of Clinical Hepatology
2022;38(6):1341-1346
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether lidocaine can reverse Kupffer cell dysfunction in diabetic mice, as well as the mechanism of lidocaine in affecting liver abscess formation by improving the phagocytic function of Kupffer cells. Methods C57BLKS/J db/db mice were divided into diabetes control group and diabetes+lidocaine group, and C57BLKS/J db/m mice were divided into non-diabetes control group and non-diabetes+lidocaine group, with 5 mice in each group. All mice were fed with the suspension of Klebsiella pneumoniae . Kupffer cells were collected from each group and were cultured in vitro; an electron microscope was used to measure the change in ultrastructure, and Kupffer c ells were measured in terms of the levels of inflammatory mediators, the expression level of intercellular adhesion molecule-1 (ICAM-1), the chemotactic function of neutrophils, and phagocytic function; liver abscess formation was also observed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the non-diabetic mice, the diabetic mice had significant reductions in mitochondria and rough endoplasmic reticulum, endoplasmic reticulum dilation, mitochondrial swelling, and an increase in lipid droplets in Kupffer cells. Compared with the non-diabetes control group, the diabetes control group had significant increases in the levels of nitric oxide (NO) (4.95±0.06 μmol/L vs 1.34±0.13 μmol/L, P < 0.05), interleukin-6 (IL-6) (740.04±8.58 pg/mL vs 515.77±4.62 pg/mL, P < 0.05), tumor necrosis factor-α (TNFα) (774.23±7.98 pg/mL vs 461.51±1.76 pg/mL, P < 0.05), interferon gamma (IFNγ) (842.33±14.79 pg/mL vs 542.47±6.75 pg/mL, P < 0.05), and ICAM-1 (2.40±0.02 vs 1.33±0.01, P < 0.05) in Kupffer cells, a significant increase in neutrophil chemotaxis (100.80±10.18 vs 13.80±3.70, P < 0.05), and a significant reduction in phagocytic capacity (9.86±1.82 vs 60.00±3.54, P < 0.05), with no effect on liver abscess formation (40% vs 0, P > 0.05). Compared with the diabetes control group, the diabetes+lidocaine group had significant reductions in the levels of NO (3.35±0.28 μmol/L vs 4.95±0.06 μmol/L, P < 0.05), IL-6 (688.42±36.34 pg/mL vs 740.04±8.58 pg/mL, P < 0.05), TNFα (631.15±4.30 pg/mL vs 774.23±7.98 pg/mL, P < 0.05), IFNγ (704.56±3.64 pg/mL vs 842.33±14.79 pg/mL, P < 0.05), and ICAM-1 (1.50±0.02 vs 2.40±0.02, P < 0.05) in Kupffer cells, a significant reduction in neutrophil chemotaxis (33.40±5.60 vs 100.80±10.18, P < 0.05), and a significant increase in phagocytic capacity (49.20±2.59 vs 9.86±1.82, P < 0.05), with no effect on liver abscess formation (0 vs 40%, P > 0.05). Conclusion Lidocaine can inhibit Kupffer cell inflammatory response and improve the phagocytic function of Kupffer cells in diabetic mice, thereby exerting a protective effect on Kupffer cells, but it had no effect on liver abscess formation.
