To explore the mechanism of remimazolam improving learning and memory ability and brain injury in postoperative cognitive impairment (POCD) mice by regulating NOD-like receptor heat protein domain associated protein 3 (NLRP3).

The C57BL/6J mice were divided into sham group (exposure of the tibia only without truncation), model group (tibia ampution method to construct POCD model), oe-NC group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NC), oe-NLRP3 group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NLRP3), experimental-L, -M, -H groups (after modeling, 5, 10, 15 mg·kg^-1 remimazolam was respectively given intraperitoneal injection), 12 rats per group. For the treated mice, the Morris water maze and step - down test were used to evaluate their learning and memory abilities. The expression levels of NLRP3, interleukin-1β (IL-1β), IL-10 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of reactive oxygen species (ROS) was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and the level of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence.

The platform crossing times of sham operation group, model group and experimental-L, -M, -H groups were (4.58±0.91), (0.73±0.15), (0.92±0.18), (1.58±0.31) and (2.75±0.55), respectively; the error times were (0.50±0.11), (2.08±0.41), (1.75±0.35), (1.58±0.31) and (1.25±0.25), respectively; the relative expression levels of NLRP3 mRNA were 1.00±0.15, 3.51±0.69, 2.94±0.59, 2.57±0.51 and 1.91±0.38, respectively; the relative expression levels of IL-1β mRNA in sham operation group, model group, experimental-H group, control group and oe-NLRP3 group were 1.00±0.17, 2.72±0.54, 1.87±0.37, 1.91±0.38 and 2.66±0.53, respectively; the relative expression levels of IL-10 mRNA were 1.00±0.16, 0.51±0.10, 0.78±0.15, 0.73±0.15 and 0.56±0.11, respectively; the relative expression levels of TNF-α mRNA were 1.00±0.21, 3.08±0.61, 1.77±0.35, 1.82±0.36 and 2.65±0.53, respectively; the relative fluorescence intensities of ROS were 1.00±0.16, 7.22±1.45, 3.05±0.61, 3.13±0.63 and 6.75±1.31, respectively; the relative fluorescence intensities of GFAP were 1.00±0.18, 6.71±1.13, 3.38±0.63, 3.50±0.72 and 5.94±1.19, respectively. The above indexes in the sham operation group were compared with the model group, the above indexes in the experimental-H group were compared with the model group, the above indexes in the oe-NLRP3 group were compared with the control group, and the differences were statistically significant (all P<0.05).

Remimazolam improves postoperative cognitive function in mice by a mechanism that may be related to the inhibition of neuroinflammatory and oxidative stress damage by down-regulating NLRP3 expression.