Tanshinone IIA alleviates early brain injury after subarachnoid hemorrhage in rats by inhibiting the activation of NF-κB/NLRP3 inflammasome

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The abnormal activation of the NF-κB/NLRP3 signaling pathway is closely related to early brain injury after subarachnoid hemorrhage (SAH). Targeting the NLRP3-inflammasome has been considered an efficient therapy for the local inflammatory response after SAH. Tanshinone ⅡA (Tan ⅡA), a major component extracted from Salvia miltiorrhiza, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the effect and mechanism of Tan ⅡA on early brain injury after SAH. In vivo SAH injury was established by endovascular perforation technique in Sprague-Dawley rats. Limb-placement test and corner turning test were used to measure the behavior. TUNEL staining, HE staining, and immunofluorescence were used to evaluate the nerve damage. RT-qPCR was used to quantify the levels of inflammatory factors. Western blot was performed for the activation of the NF-κB/Nod-like receptor family-pyrin domain-containing 3 (NLRP3) pathway. An in vitro SAH model was used to validate the conclusion. We found that the neurobehavioral impairment and cerebral edema in SAH model rats given Tan ⅡA were alleviated. Further study demonstrated that Tan ⅡA could inhibit SAH-secondary neuronal apoptosis around hematoma and alleviate brain injury. Tan ⅡA down-regulated the expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), and TNF-α, and inhibited the activation of NF-κB. And the overexpression of pro-inflammatory factors NLRP3, IL-1β, and IL-18 induced after SAH was also reversed by Tan ⅡA. In conclusions, Tan ⅡA could inhibit the NF-κB/NLRP3 inflammasome activation to protect and ameliorate SAH-followed early brain injury, and may be a preventive and therapeutic strategy against SAH.