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Objective:To evaluate the effect of esketamine on acute kidney injury (AKI) in the rats with sepsis and the role of autophagy.Methods:Forty SPF healthy adult male Sprague-Dawley rats, weighing 200-240 g, were divided into 5 groups ( n=8 each) by a random number table method: control group (Con group), esketamine group (Con+ Ket group), sepsis group (lipopolysaccharide [LPS] group), sepsis plus esketamine group (LPS+ Ket group), and sepsis plus esketamine plus 3-methyladenine (3MA) group (LPS+ Ket+ 3MA group). The model of AKI was established by intraperitoneal injection of LPS in anesthetized rats.Normal saline 10 ml/kg was intraperitoneally injected in Con group.In Con+ Ket group, normal saline 10 ml/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg was injected via the tail vein.LPS 10 mg/kg was intraperitoneally injected in LPS group.In LPS+ Ket group, LPS 10 mg/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg was injected via the tail vein.In LPS+ Ket+ 3MA group, LPS 10 mg/kg was intraperitoneally injected, and 30 min later esketamine 10 mg/kg and 3-MA 15 mg/kg were injected via the tail vein.The rats were anesthetized at 24 h after intraperitoneal injection of LPS and then sacrificed, and renal tissues were removed for microscopic examination of the pathological changes which were scored and for determination of contents of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay) and expression of LC3, P62 and Beclin-1 (by Western blot). Results:Compared with Con group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly increased, LC3-Ⅱ/LC3-Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of P62 was up-regulated in LPS group ( P<0.05). Compared with LPS group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly decreased, LC3-Ⅱ/LC3-Ⅰ ratio was increased, the expression of Beclin-1 was up-regulated, and the expression of P62 was down-regulated in LPS+ Ket group ( P<0.05). Compared with LPS+ Ket group, the score for pathological damage to renal tissues and contents of NLRP3, ASC, caspase-1, IL-1β and IL-18 were significantly increased, LC3-Ⅱ/LC3-Ⅰ ratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of P62 was up-regulated in LPS+ Ket+ 3MA group ( P<0.05). Conclusion:Esketamine can reduce AKI and autophagy is involved in the process, which is related to inhibiting the activation of NLRP3 inflammasomes and decreasing inflammatory responses in rats with sepsis.
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Objective To investigate the effects of repeated intraperitoneal dexmedetomidine on the cognitive function in rats with chronic cerebral ischemia.Methods Forty-eight male Sprague-Dawley rats,aged 3-4months,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) ∶ sham operation group (group S),chronic cerebral ischemia group (group IS),dexmedetomidine treatment 1 group (group DXM1) and dexmedetomidine treatment 2 group (group DXM2).Dexmedetomidine 5 μg/kg was injected intraperitoneally at 30 min before occlusion of bilateral common carotid arteries and 3,12,24 and 48 h after occlusion in group DXM1,and at 3,12,24 and 48 h after occlusion in group DXM2.The cognitive function was assessed by Morris water maze 2 weeks after occlusion.The apoptosis was examined by TUNEL.The expression of Bcl-2 protein in hippocampus was detected by Western blot.Results Compared with group S,the escape latency was significantly prolonged from 2nd day to 5th day after the place navigation test in group IS and on 2nd day after Morris water maze test in groups DXM1 and DXM2,and the time of staying in 1 st quadrant was significantly shortened,the apoptotic rate was increased,and the expression of Bcl-2 was up-regulated in groups IS,DXM1 and DXM2 (P ＜ 0.05).Compared with group IS,the escape latency was significantly shortened from 3rd day to 5th day after the place navigation