Vinpocetine Attenuates Ischemic Stroke Through Inhibiting Nlrp3 Inflammasome Expression In Mice

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY(2021)

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摘要
Ischemic stroke is the leading cause of globe death and permanent disability, but its therapeutic strategies are limited. Over the past decades, multiprotein complexes called inflammasomes have been shown as promising targets in ischemic stroke. Here, we examined vinpocetine (Vinp), a synthetic drug, playing a neuroprotective role against ischemic stroke in mice through regulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Middle cerebral artery occlusion/reperfusion (MCAO/R) was applied to mimic ischemic stroke in vivo. Vinp was administrated by intraperitoneal injection with different dose (5 or 10 mg/kg) 1 hour after reperfusion. Then, neurological assessment and infarct size were performed, and interleukin-1 beta (IL-1 beta) and IL-18 levels were evaluated using ELISA. The levels of NLRP3 inflammasome components and its upstream nuclear factor-kappa B (NF-kappa B) were determined using real-time PCR or Western blot. The experimental results indicated that posttreatment with Vinp decreased cerebral infarct size, improved behavior recover, reduced NLRP3 inflammasome expression, and suppressed the transfer of NF-kappa B to nucleus and proinflammatory cytokine release in middle cerebral artery occlusion/reperfusion mice. In conclusion, this study demonstrates that Vinp alleviates ischemic stroke by regulating levels of NLRP3 inflammasome, NF-kappa B, and proinflammatory cytokines in vivo, offering an alternative medication for ischemic stroke associated with inflammation.
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关键词
ischemic stroke, vinpocetine, NLRP3 inflammasome
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