Division of Pediatric Critical Care Medicine, Department of Pediatrics, Chang Gung Memorial Hospital at Linko, Taiwan.
College of Medicine, Chang Gung University, Taiwan.
Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221090021. doi: 10.1177/03946320221090021.
Sepsis caused by aggressive infection is a severe clinical problem with an increasing incidence worldwide. Toll-like receptors and their common adapter myeloid differentiation factor 88 (MyD88) can activate immune responses by recognizing a foreign microbe's product. This study aimed to identify the different time expression of TLR four signaling pathway in an experimental rodent model of polymicrobial sepsis. A randomized animal study was investigated in rats with septic peritonitis induced by cecal ligation and puncture (CLP). The expressions of MyD88-dependent pathway biomarkers, including MyD88, nuclear factor-κB (NF-κB), and serum tumor necrosis factor-α (TNF-α), were analyzed and compared to the sham controls at the different time points after CLP surgery. CLP-induced sepsis increased liver MyD88 mRNA expression and protein expression compared to the control groups at 2 h after surgery. The MyD88 mRNA and protein expressions in rats with CLP-induced sepsis marked increased at 4 and 6 h, and their NF-κB activities and serum TNF-α levels also increased at 4 h after CLP surgery (both < .05). The different serial expression of MyD88-ependent pathway during sepsis may be used as biomarkers during sepsis. These results may provide further helpful information for using pro-inflammatory biomarkers of innate immunity such as MyD88 and TNF-α in clinical sepsis or related abdominal surgical emergency in the future.
侵袭性感染导致的脓毒症是一种严重的临床问题，全球发病率呈上升趋势。Toll 样受体及其共同衔接分子髓样分化因子 88（MyD88）可以通过识别外来微生物产物来激活免疫反应。本研究旨在鉴定多微生物脓毒症实验啮齿动物模型中 TLR 四条信号通路的不同时间表达。通过盲肠结扎穿刺（CLP）诱导的腹膜炎对大鼠进行随机动物研究。在 CLP 手术后的不同时间点，分析并比较 MyD88 依赖性途径生物标志物（包括 MyD88、核因子-κB（NF-κB）和血清肿瘤坏死因子-α（TNF-α））的表达，与假手术对照组进行比较。与对照组相比，CLP 诱导的脓毒症大鼠在手术后 2 小时时肝 MyD88 mRNA 表达和蛋白表达增加。CLP 诱导的脓毒症大鼠的 MyD88 mRNA 和蛋白表达在 4 和 6 小时时显著增加，其 NF-κB 活性和血清 TNF-α 水平在 CLP 手术后 4 小时也增加（均<0.05）。脓毒症期间 MyD88 依赖性途径的不同连续表达可用作脓毒症期间的生物标志物。这些结果可能为未来在临床脓毒症或相关腹部外科急症中使用先天免疫的促炎生物标志物（如 MyD88 和 TNF-α）提供进一步的有益信息。
