Roles of MyD88 and TRIF in cardiac dysfunction during sepsis

Abstract

To investigate the roles of myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF) in sepsis-induced myocardial dysfunction, and to analyze whether strain rate (SR) can be early sensitive evaluation for septic heart failure. Sixty-four healthy male C57BL/6 mice were divided into four groups by random number table (n = 16 in each group): sham group, cecum ligation and puncture (CLP)-induced sepsis model group, anti-MyD88 group and anti-TRIF group. The anti-MyD88 group and anti-TRIF group were injected with 5 μL/g of anti-MyD88 antibody or anti-TRIF antibody through the tail veins 2 hours before CLP. Eight animals in each group were used to observe the survival of 24 hours, and the other 8 myocardial tissues were harvested for examination. The cardiac function was evaluated by echocardiography before and 6 hours and 12 hours after operation. The mRNA expressions of MyD88, TRIF and inflammatory factors in myocardium were measured by polymerase chain reaction (PCR) at 24 hours after operation, and the degree of neutrophils infiltration was detected by myeloperoxidase (MPO) activity. The number of 24-hour survive in anti-MyD88 group and anti-TRIF group were higher than that in CLP group (number: 4, 3 vs. 2, P = 0.044, P = 0.047). Compared with sham group, the cardiac function was significantly decreased, the mRNA expressions of myocardial tissues MyD88, TRIF, interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased, and the infiltration of neutrophils were obvious in CLP group. Compared with CLP group, the left ventricular short axis fractional shortening rate (FS) and SR were significantly increased after 12 hours in anti-MyD88 group and anti-TRIF group [FS: (49.52±1.78)%, (49.89±1.49)% vs. (41.11±1.63)%, SR (s-1): 17.63±2.16, 17.85±1.64 vs. 12.55±1.84]; the mRNA expressions of MyD88, TRIF and inflammatory factors were significantly decreased [MyD88 mRNA (A value): 0.463±0.046, 0.505±0.048 vs. 0.638±0.102, TRIF mRNA (A value): 0.413±0.031, 0.410±0.021 vs. 0.625±0.057, IL-1 mRNA (A value): 0.569±0.101, 0.570±0.091 vs. 0.946±0.171, IL-6 mRNA (A value): 0.551±0.143, 0.431±0.157 vs. 0.850±0.194, TNF-α mRNA (A value): 0.471±0.082, 0.444±0.093 vs. 0.707±0.094]; and the infiltration of neutrophils were significantly decreased [MPO (U/L): 62.34±2.60, 60.87±2.40 vs. 73.83±4.90], with statistically significant differences (all P < 0.05). There was no statistical difference in above parameters between the anti-MyD88 group and anti-TRIF group (all P > 0.05). Blocking MyD88 and TRIF expression play significant and similar roles in protecting cardiac deterioration from sepsis by attenuating cytokine release, reducing neutrophil infiltration. SR can sensitively assess septic cardiac dysfunction.