Effects and mechanisms of oliceridine fumarate on postoperative cognitive dysfunction in elderly rats through TLR4/NF-κB pathway
- VernacularTitle:富马酸奥赛利定通过TLR4/NF-κB通路改善老年大鼠术后认知功能障碍的作用及机制
- Author:
Dong XIE
1
;
Xiaoying GENG
2
;
Yushan ZHU
3
;
Zhengxiang LI
1
;
Hengjie YUAN
1
Author Information
1. Dept.of Pharmacy，Tianjin Medical University General Hospital，Tianjin 300052，China
2. Dept. of Pharmacy，Tianjin 272 Hospital，Tianjin 300020，China
3. School of Pharmacy，Tianjin Medical University，Tianjin 300070，China
- Publication Type:Journal Article
- Keywords:
oliceridine fumarate;
elderly rats;
postoperative cognitive dysfunction;
TLR4/NF-κB pathway;
neuroinflammation
- From:
China Pharmacy
2026;37(11):1434-1439
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate （TRV130） in improving postoperative cognitive dysfunction （POCD） in elderly rats based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway. METHODS Rats were randomly divided into the control group （normal saline）， the model group （normal saline）， the TRV130 group （2.8 mg/kg）， the TLR4/NF-κB pathway inhibitor （TAK-242） group （3 mg/kg）， the β -arrestin inhibitor （Barbadin） group （3 mg/kg）， and the traditional opioid drug （morphine） group （2.8 mg/kg）， with 15 rats in each group. Except for the control group， POCD models were established in all other groups. From the first day after surgery， drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration， the pathological damage of hippocampal tissue was observed； the cognitive function， serum inflammatory factor levels， hippocampal neurons apoptosis rate， and the expression of ionized calcium-binding adapter molecule 1 （Iba-1）， glial fibrillary acidic protein （GFAP）， and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group， the neurons in the CA1 region of the hippocampus were disordered and sparse， with decreased number， pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group， the escape latency， serum levels of tumor necrosis factor α （TNF-α）， interleukin-6 （IL-6）， and IL-1β， hippocampal neurons apoptosis rate， average fluorescence intensities of Iba-1 and GFAP， mRNA expression levels of TLR4 and NF-κB p65， and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group （ P ＜0.05）； the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased （ P ＜0.05）. Compared with the model group， the cognitive function， pathological， inflammatory， and apoptosis-related indicators were significantly improved in the TRV130 group， TAK-242 group， and Barbadin group （ P ＜0.05）； the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group （ P ＜0.05）. CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.
