目的 探讨髓样分化因子88(MyD88)和β-干扰素TIR结构域衔接蛋白(TRIF)在脓毒症所致心肌功能障碍中的作用;分析应变率(SR)能否早期敏感评价脓毒症性心功能不全.方法 按随机数字表法将64只健康雄性C57BL/6小鼠分为假手术(Sham)组、盲肠结扎穿孔术(CLP)致脓毒症模型组、抗MyD88组和抗TRIF组,每组16只.抗MyD88组和抗TRIF组分别于术前2 h经尾静脉注射抗MyD88抗体5μL/g或抗TRIF抗体5μL/g.每组8只动物用于观察24 h存活情况;另8只取心肌组织备检.于术前及术后6 h和12 h用超声心动图评价心功能;术后24 h用聚合酶链反应(PCR)测定心肌组织MyD88、TRIF和炎性因子的mRNA表达,通过检测髓过氧化物酶(MPO)活性了解心肌中性粒细胞浸润程度.结果 抗MyD88组和抗TRIF组小鼠24 h存活动物数多于CLP组(只:4、3比2,P值分别为0.044和0.047).与Sham组比较,CLP组心功能明显下降,心肌组织MyD88、TRIF、白细胞介素(IL-1、IL-6)、肿瘤坏死因子-α(TNF-α)的mRNA表达明显升高,中性粒细胞浸润明显.与CLP组比较,抗MyD88组和抗TRIF组术后12 h左室短轴缩短率(FS)、SR明显升高〔FS:(49.52±1.78)%、(49.89±1.49)%比(41.11±1.63)%,SR(s-1):17.63±2.16、17.85±1.64比12.55±1.84〕,MyD88、TRIF、炎性因子的mRNA表达明显降低〔MyD88 mRNA(A值):0.463±0.046、0.505±0.048比0.638±0.102,TRIF mRNA(A值):0.413±0.031、0.410±0.021比0.625±0.057,IL-1 mRNA(A值):0.569±0.101、0.570±0.091比0.946±0.171,IL-6 mRNA(A值):0.551±0.143、0.431±0.157比0.850±0.194,TNF-αmRNA(A值):0.471±0.082、0.444±0.093比0.707±0.094〕,中性粒细胞浸润明显减少〔MPO(U/L):62.34±2.60、60.87±2.40比73.83±4.90〕,差异均有统计学意义(均P〈0.05).抗MyD88组与抗TRIF组各指标比较差异无统计学意义(均P〉0.05).结论 阻断MyD88和TRIF表达可以减少炎性因子释放和中性粒细胞浸润,?
Objective 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.Methods 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 5μL/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.Results 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 decrea