Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway北大核心CSCD

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg -1 ? kg-1 ? d-1 ) baicalin group, high-dose (120 mg-1 ? kg-1 ? d-1 ) baicalin group and minocycline group (36 mg-1 ? kg-1 ? d-1 ). The learning and memory ability of rats were assessed by Morris water maze. The mRNA expressions of tumor necrosis Factor-α(TNF-α), interleukin-6 (IL-6), interleukin-1β(IL-1β) were detected by real-time quantitative PCR, the protein expressions of TLR4, MyD88, N F-Κ B p65, p-NF-κB p65 and nucleus/cytoplasm NF-ΚB p65 were detected by Western blot, and NF-ΚB p65 transfering from cytoplasm to nucleus and the activation of microglia were measured by immunofluorescence. Results Compared with the sham operation group, animals in the model group showed decreased learning and memory capacity, increased mRNA expression of TNF-α, IL-6 and IL-1κ, up-regulated protein expressions of TLR4 and MyD88, the ratio of p-NF-κB p65/NF-κB p65 and the nucleus/cytoplasm ratio of NF-ΚB p65, enhanced expression of NF-KB p65 in nucleus and the activation of microglias. Compared with the model group, baicalin group and minocycline group improved the learning and memory capacity of AD rats, decreased the mRNA expression of TNF-α, IL-6 and IL-1β, down-regulated the protein expressions of TLR4 and MyD88, the p-NF-ΚB P65/NF-KB p65 ratio and the nucleus/cytoplasm ratio of NF-KB p65, and reduced the expression of NF-KB p65 in nucleus and the activation of microglias. Conclusion Baicalin may exert neuroprotective effects by inhibiting the TLR4/MyD88/NF-KB signaling pathway and neuroinflammation response in the AD brain. © 2023 Publication Centre of Anhui Medical University. All rights reserved.