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Updated: Sep 29, 2025
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Correlation between microRNA-320 and postoperative delirium in patients undergoing tibial fracture internal fixation
Bin Wang1, Zeng Yin2, Yanan Lin3
1Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, NO. 5 Donghai Middle Road, Qingdao, 266071, Shandong, China.
Background:
Although the incidence of postoperative delirium (POD) in the elderly after surgery are rising as individuals are living longer, the pathogenesis of POD remains poorly understood. It has been suggested that miRNA-320 may play a role in POD based on animal study and human study.
Methods:
We first carried out an animal study, and designed and conducted a human study based on the result of animal study. The aged rats were randomly assigned to five groups: the control (C), anesthesia and surgery (AS), saline (NS), agomir-320 (AG), and antagomir-320 (AT) groups. Postoperative spatial learning and memory in rats were analyzed by the Morris water maze and the open field tests. The plasma levels of insulin-like growth factor-1 (IGF-1), amyloid precursor protein (APP) proteins, miRNA320 and IGF-1mRNA were measured by ELISA and qRT-PCR, respectively. A total of 240 Chinese Han patients over 65 years who underwent tibial fracture internal fixation were included in the PNDABLE study. POD cases and non-POD controls (1:1 matched) were selected by an anesthesiologist using Confusion Assessment Method.
Results:
For Group AS, the escape latency was significantly longer and the ratio of time spent in the target quadrant was significantly reduced, APP and miR-320 were upregulated and IGF-1mRNA was downregulated compared with Group C. For Group AG, the escape latency was significantly longer and the ratio of time spent in the target quadrant was significantly reduced, APP and miR-320 were upregulated and IGF-1mRNA was downregulated compared with Group AS. For Group AT, the escape latency was significantly reduced and the ratio of time spent in the target quadrant was significantly longer, APP and miR-320 were downregulated and IGF-1mRNAwas upregulated compared with Group AS. Compared with NPOD patients, the expressions of plasma miR-320 and APP protein were increased and the expression of plasma IGF-1 mRNA was decreased in POD patients after surgery.
Conclusions:
MiRNA-320 might play a role in up-regulating the levels of IGF-1mRNA and APP protein, which offered a new target for POD treatment.
Trial Registration:
Correlation of perioperative neurocognitive disorders with lifestyle and biomarkers. ChiCTR2000033439 . Registered 1 June 2020.
Insights
MicroRNA-320 (miRNA-320) may contribute to postoperative delirium (POD) by increasing insulin-like growth factor-1 (IGF-1) and amyloid precursor protein (APP). Targeting miRNA-320 could offer a new therapeutic strategy for POD.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Postoperative delirium (POD) incidence is rising in the elderly, yet its pathogenesis remains unclear.
- MicroRNA-320 (miRNA-320) is a potential factor in POD, suggested by preliminary animal and human studies.
Purpose of the Study:
- To investigate the role of miRNA-320 in the pathogenesis of POD.
- To explore miRNA-320 as a potential therapeutic target for POD.
Main Methods:
- An animal study using aged rats (control, anesthesia/surgery, saline, agomir-320, antagomir-320) assessed spatial learning and memory.
- Plasma levels of insulin-like growth factor-1 (IGF-1), amyloid precursor protein (APP), miRNA-320, and IGF-1 mRNA were measured.
- A human study (PNDABLE) included 240 elderly patients undergoing tibial fracture fixation, comparing POD cases with matched controls.
Main Results:
- In rats, anesthesia/surgery upregulated miR-320 and APP while downregulating IGF-1 mRNA, impairing cognitive function.
- Agomir-320 mimicked these effects, while antagomir-320 reversed them.
- POD patients exhibited increased plasma miR-320 and APP, and decreased IGF-1 mRNA compared to controls.
Conclusions:
- MiRNA-320 appears to play a role in POD pathogenesis by potentially upregulating IGF-1 mRNA and APP protein.
- Targeting miRNA-320 presents a novel therapeutic avenue for managing POD.
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