Study on the Mechanism of Eerdun Wurile's Effects on Post-operative Cognitive Dysfuntion by the TLR4/NF-κB Pathway

Abstract

Abstract Aims: The object of our work was to observe whether the Mongolian medicine Eerdun Wurile (EW) improve POCD by affecting the TLR4/NF-κB. Methods: Mice (6–8 week-old male C57BL/6J) were selected to establish an animal model of POCD by combining intracerebroventricular injection of lipopolysaccharide and nephrectomy; EW formulation and EW basic formulation were administered intra-gastrically for 7 consecutive days. The cognitive performance was assessed by Morris water maze test. H&E staining was examined to detect alterations in hippocampal tissue. Immunohistochemical staining was performed to evaluate MyD88, NF-κB, TLR4, iNOS, and IBA-1 expressions; Western blotting and RT-qPCR were performed to evaluate MyD88, NF-κB and TLR4. The expressions of IL-6, IL-1β, and TNF-α were evaluated by ELISA. Results: Intracerebroventricular injection of lipopolysaccharide combined with nephrectomy induced cognitive dysfunction in mice, stimulated TLR4/NF-κB and microglia, and promoted the secretion of murine TNF-α, IL-1β and IL-6. EW formulation and EW basic formulation treatment are able to suppress the TLR4/NF-κB pathway activation and microglia, and the serum cytokine secretions related to proinflammation, and restore the cognitive performance. Conclusion: EW formulation and EW basic formulation can improve POCD in mice, and TLR4/NF-κB pathway seems to be one of the important mechanisms in EW's improvement of POCD.