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.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*