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Effect of VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation / 中华麻醉学杂志
Chinese Journal of Anesthesiology ; (12): 229-232, 2020.
Article in Chinese | WPRIM | ID: wpr-869811
ABSTRACT

Objective:

To evaluate the effect of selective inhibitor of caspase-1 VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation (HSR).

Methods:

Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 4 groups ( n=12 each) using a random number table

method:

sham operation group (S group), HSR group (H group), VX-765 group (V group), and solvent control group (C group). The rats in H, V and C groups were subjected to hemorrhage by bleeding from femoral vein to achieve mean arterial pressure of 25-35 mmHg which was maintained at this level for 60 min followed by resuscitation with shed blood within 15 min to restore blood pressure, and normal saline was infused when needed.VX-765 1 mg/kg and 0.4% polyethylene glycol 1 mg/kg were intravenously injected via the femoral vein immediately after the end of resuscitation in V and C groups, respectively.Six rats in each group were selected and sacrificed at 12 h after the end of resuscitation, and the cerebral cortex was removed for determination of neuronal pyroptosis (by immunofluorescence) and degree of cortical edema (using T2-weighted imaging). Cognitive function was measured by open field test on day 7 after resuscitation in the rest 6 rats in each group.

Results:

Compared with S group, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly increased, the distance in the central square and the number of standing on the back legs were decreased on day 7 after resuscitation, and the time spent in the central square was shortened in H, V and C groups ( P<0.05). Compared with H and C groups, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly decreased, the distance in the central square and the number of standing on the back legs were increased on day 7 after resuscitation, and the time spent in the central square was prolonged in V group ( P<0.05).

Conclusion:

VX-765 can improve the cognitive function, and the mechanism may be associated with inhibiting pyroptosis in cortical neurons in a rat model of HSR.
Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2020 Type: Article