别孕烯醇酮对老年雄性小鼠术后谵妄的 防治作用及其机制.

Objective To observe the preventive and therapeutic effect of intraperitoneal and subcutaneous injection of allopregnanolone (Allo) on postoperative delirium (POD) in aged male mice and to explore its possible mechanism. Methods Ninety-six 6-month-old male C57BL/6J mice were randomly divided into groups A, B, C and control group, with 24 in each. Mice in the control group were fed normally, and mice in the groups A, B and C underwent internal fixation of tibial fracture of right lower limb (POD animal model preparation method is commonly used). Mice in the group A were intraperitoneally injected with 8 mg/kg allopregnenolone at 1 h after surgery, and then were subcutaneously injected with 8 mg/kg allopregnenolone at 6, 24 and 48 h after surgery, respectively. Mice in the group B were intraperitoneally injected with 2-hydroxypropyl-β-cyclodextrin at 1 h after surgery, and subcutaneously injected with 2-hydroxypropyl-β-cyclodextrin at 6, 24 and 48 h after surgery, respectively. Mice in the group C were not given any drugs after surgery. Morris water maze test was used to evaluate the spatial learning and memory ability of mice before surgery and at the 1, 3 and 7 days after surgery, respectively. After the test, six mice were randomly killed in each group. Hippocampal tissues were taken to detect inflammatory factors and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), nuclear factor κB (NF-κB), and NOD-like receptor protein 3 (NLRP3) pathway-related proteins in the hippocampal tissues of mice in each group. Results Compared with the control group, the escape latency of mice in group C was longer and the number of platform crossing was smaller on the 1st, 3rd and 7th days after operation (all P<0. 05). Compared with the group C, the escape latency of mice in the group A was shorter and the number of platform crossing was lager on day 1, 3 and 7 after operation (all P<0. 05). Compared with the control group, the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), p-p38MAPK, NF-κB, and NLRP3 in the hippocampal tissues of group C were higher on day 1, 3 and 7 after surgery (all P<0. 05). Compared with the group C, the expression levels of TNF-α, IL-1β, p-p38MAPK, NF-κB and NLRP3 in the hippocampal tissues of the group A were lower on day 1, 3 and 7 after surgery (all P<0. 05). Conclusion Intraperitoneal and subcutaneous injection of allopregnenolone can reduce POD after internal fixation of tibial fracture of right lower limb in aged male mice probably by inhibiting the expression levels of TNF-α, IL-1β, p-p38MAPK, NF-κB, and NLRP3 in the hippocampal tissues. [ABSTRACT FROM AUTHOR]