Effect of exogenous miR-181b on postoperative cognitive dysfunction in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of exogenous miR-181b on postoperative cognitive dysfunction ( POCD) in mice. Methods A total of 108 clean-grade healthy male C57BL∕6 mice, weighing 25-30 g, were divided into 4 groups ( n=27 each) using a random number table method: control group ( group C) , POCD group, miR-181b agonist agomir group ( group Ag) , and agomir negative control group ( group AC) . POCD was induced by open tibial fracture in 2. 1％ isoflurane-anesthetized mice. A total vol-ume of miR-181b agomir 4μl ( 0. 25 nmol∕μl) was injected into bilateral hippocampi at 2 days before estab-lishing the model in group Ag. Agomir negative control solution 4μl was given at 2 days before establishing the model in group AC. Eighteen mice were selected at days 1, 3 and 7 after surgery, and contextual fear conditioning test was performed to assess cognitive function. Nine mice in each group were sacrificed at 6, 12 and 24 h after surgery ( 3 mice at each time point) , and the hippocampus was isolated for determination of miR-181b expression ( by quantitative real-time polymerase chain reaction) and interleukin-1β ( IL-1β) and tumor necrosis factor-α ( TNF-α) contents ( by enzyme-linked immunosorbent assay) . Results Com-pared with group C, the percentage of time spent freezing in the contextual fear conditioning test was signifi-cantly decreased at 1, 3 and 7 days after surgery, and the expression of miR-181b was down-regulated and the contents of IL-1β and TNF-α were increased at 6, 12 and 24 h after surgery in POCD and AC groups( P<0. 05) . Compared with POCD and AC groups, the percentage of time spent freezing in the contextual fear conditioning test was significantly increased 1, 3 and 7 days after surgery, and the expression of miR-181b was up-regulated and the contents of IL-1βand TNF-αwere decreased at 6, 12 and 24 h after surgery in group Ag ( P<0. 05). Conclusion Exogenous miR-181b can mitigate POCD, and the mechanism may be related to inhibiting inflammatory responses in the hippocampus of mice.