Effect of vitamin K 2 on traumatic brain injury and the relationship with NLRP3 inflammasomes in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of vitamin K 2 on traumatic brain injury (TBI) and the relationship with nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes in rats. Methods:Thirty-six SPF healthy male Sprague-Dawley rats, weighing 280-300 g, were divided into 3 groups ( n=12 each) by a random number table method: sham operation group (group Sham), group TBI and TBI plus vitamin K 2 group (group TBI+ VK 2). The TBI model was developed using modified Feeney′s method.In TBI+ VK 2 group, vitamin K 2 400 mg/kg (dissolved in dimethyl sulfoxide) was intraperitoneally injected at 30 min after developing TBI model.The equal volume of dimethyl sulfoxide was intraperitoneally injected in group Sham and group TBI.The modified neurological severity score (mNSS) was measured and open field tests were performed at 24 h after development of TBI.The rats were sacrificed after the end of behavioral testing, and brains were obtained for measurement of brain water content (by wet-dry weight method), percentage of brain injury volume (by TTC assay), contents of interleukin-1β (IL-1β), IL-18 and caspase-1 in cortex on the injured side (by enzyme-linked immunosorbent assay) and expression of NLRP3, caspase-1 and IL-18 in cortex on the injured side (by Western blot). Results:Compared with group Sham, the mNSS score was significantly increased, the total distance travelled was reduced, the time spent in the central zone was shortened, the brain water content and percentage of brain injury volume were increased, the contents of IL-1β, IL-18 and caspase-1 in cortex on the injured side were increased, and the expression of NLRP3, caspase-1 and IL-18 was up-regulated in group TBI ( P<0.05 or 0.01). Compared with group TBI, the mNSS score was significantly decreased, the total distance travelled was increased, the time spent in the central zone was prolonged, the brain water content and percentage of brain injury volume were decreased, the contents of IL-1β, IL-18 and caspase-1 in cortex on the injured side were decreased, and the expression of NLRP3, caspase-1 and IL-18 was down-regulated in group TBI+ VK 2 ( P<0.05 or 0.01). Conclusions:Vitamin K 2 can reduce TBI, and the mechanism may be related to inhibition of the activation of NLRP3 inflammasomes in rats.