[Role of dendritic cells in lipopolysaccharide induced cardiac dysfunction in mice].

ABSTRACT

OBJECTIVE: To observe the role of dendritic cells (DC) in lipopolysaccharide (LPS)-induced myocardial dysfunction in mice. METHODS: Eighty wild type male C57BL/6 mice were divided into four groups, according to random number table method: sham group, DC inhibitors in control group (VAG539-sham group), LPS sepsis model group (LPS group) and DC inhibitors pretreatment group (VAG539-LPS group), 20 in each group. The cardiac dysfunction model of sepsis mice was established by LPS intraperitoneal injection; the sham group was injected with the same dose of normal saline. VAG539-sham group and VAG539-LPS group were injected with the DC inhibitor VAG539 (30 mg/kg, twice per day, for 2 days) before injection with normal saline or LPS, respectively. Ten mice in each group were used to observe the 14-day survival rate. Mean arterial pressure (MAP) of the remaining 10 mice was measured through the small animal tail artery cannula; the cardiac function [including the heart rate (HR), left ventricular ejection fraction (LVEF) and short axial shortening rate (FS)] were evaluated by small animal echocardiography; the aggregation and maturation of myocardial DC were detected by flow cytometry; and serum inflammatory factors [including tumor necrosis factor-α (TNF-α), interleukins (IL-12, IL-6)] were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with sham group, the 14-day cumulative survival rate in LPS group was significantly reduced, while HR, MAP, LVEF and FS were significantly decreased, and the number of DC in myocardial tissues was significantly increased, and the levels of serum inflammatory factors were increased significantly. The 14-day cumulative survival rate in VAG539-LPS group was significantly higher than that in the LPS group (55% vs. 15%, P < 0.05). Compared with LPS group, after pretreatment by VAG539, the HR, MAP, LVEF and FS were significantly increased [HR (bpm) 610±25 vs. 556±28, MAP (mmHg, 1 mmHg = 0.133 kPa) 68±6 vs. 42±2, LVEF 0.48±0.02 vs. 0.30±0.03, FS (34±3)% vs. (14±2)%, P < 0.05]; the number of DC in myocardial tissue was significantly decreased from 6.5% to 3.7%; the level of serum inflammatory factors were significantly decreased [TNF-α (ng/L) 192.00±25.45 vs. 291.34±23.12, IL-12 (ng/L) 58.44±12.37 vs. 78.43±11.24, IL-6 (ng/L) 46.97±8.12 vs. 149.12±15.45, all P < 0.05]. CONCLUSIONS: Sepsis can cause cardiac dysfunction, and it can play an important role by inhibiting the DC cell function of myocardium and reducing the expression of inflammatory factors.