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  • Title: Improvement in cerebral ischemia-reperfusion injury through the TLR4/NF-κB pathway after Kudiezi injection in rats.
    Author: Liu X, Zhang X, Wang F, Liang X, Zeng Z, Zhao J, Zheng H, Jiang X, Zhang Y.
    Journal: Life Sci; 2017 Dec 15; 191():132-140. PubMed ID: 29080695.
    Abstract:
    AIM: Kudiezi injection (KDZ) can improve the clinical outcomes of patients with stroke, but the mechanisms remain unclear. This study aimed to investigate whether KDZ could modulate the nuclear factor kappa B (NF-κB) pathways in rat models of transient middle cerebral artery occlusion (tMCAO). MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to tMCAO and randomized to Sham (sham-operated), tMCAO (tMCAO+0.9% saline), and KDZ (tMCAO+7.2mL/kg KDZ) groups. The infarct volume, brain water content, and neurological deficit were assessed 72h after reperfusion. Immunofluorescence was used to detect the expression of cleaved caspase-3 and NF-κBp65. The expression of cleaved caspase-3, NF-κB p65, TLR4, MyD88, TRAF6, and p-IκBα/IκBα was determined using Western blotting. The expression levels of TNF-α, interleukin (IL)-1β, and IL-10 in the ischemic cortex were measured using the enzyme-linked immunosorbent assay. In vitro ischemic paradigm (oxygen-glucose deprivation) was performed in SH-SY5Y cells to evaluate the effects of KDZ. KEY FINDINGS: Lower brain water content, smaller infarct volume, and better neurologic function were found in the KDZ group compared with the tMCAO group. The expression of activated caspase-3, TLR-4, TRAF6, NF-κBp65, and p-IκBα/IκBα reduced and the levels of TNF-α and IL-1β decreased in the KDZ group, with the increased IL-10 level. In SH-SY5Y cells, KDZ significantly reduced the expression of p-IκBα and IκBα, lowered the death ratio, and reversed the effects induced by caffeic acid phenethyl ester (a potent NF-κB inhibitor). SIGNIFICANCE: KDZ may function through downregulating the TLR-4-dependent NF-κB signaling pathway to protect the brain against ischemic injury.
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