背景:髋部骨折在老年人中普遍存在;然而,术后认知功能障碍(POCD)是老年髋部骨折术后可能的并发症。本研究探讨右美托咪定对老年髋部骨折术后患者POCD的影响及作用机制。
方法:回顾性研究对象为2021年10月至2022年8月新疆医科大学第五附属医院收治的老年髋部骨折患者。在手术过程中,给予右美托咪定,并收集患者的外周血样本。使用酶联免疫吸附试验(ELISA)测量炎症因子,而通过定量逆转录PCR(RT-qPCR)和Westernblot检测焦亡相关蛋白。此外,使用流式细胞术评估CD4+T细胞和CD8+T细胞的水平.建立老年大鼠髋部骨折模型,进一步研究右美托咪定对术后活动能力的影响,认知功能,大鼠的焦亡和免疫细胞。
结果:患者术后认知功能与术前水平相比没有显著改变(p>0.05)。白细胞介素-18(IL-18)的水平显着降低,Caspase-3,Gasdermin-D(GSDMD)和NLR家族Pyrin结构域包含3(NLRP3)(p<0.001),术后CD4+T细胞比例增加,CD8+T细胞减少(p<0.01)。在老年老鼠中,术后探查活动与术前状态相比增加。与术前水平相比,白细胞介素-1β(IL-1β)的水平,IL-18,Caspase-3,GSDMD,NLRP3显著下降(p<0.001),CD4+T细胞比例增加,术后CD8+T细胞比例降低(p<0.01)。
结论:尽管患者术后认知功能无明显改变,右美托咪定可能仍在减轻POCD方面发挥作用,这可能是由于其对减少免疫炎症和焦凋亡标志物的作用.需要进一步的研究来充分了解潜在的机制及其临床意义。
BACKGROUND: Hip fractures are prevalent in the elderly; however, Postoperative Cognitive Dysfunction (POCD) is a possible complication of hip fracture surgery in elderly patients. This study examines the influence and the underlying mechanism of dexmedetomidine on POCD in elderly patients following hip fracture surgery.
METHODS: The retrospective study involved elderly patients with hip fracture who were treated at the Fifth Affiliated Hospital of Xinjiang Medical University from October 2021 to August 2022. During the surgery procedures, dexmedetomidine was administrated and the peripheral blood samples were collected from the patients. Inflammatory factors were measured using Enzyme-linked immunosorbent assay (ELISA), while pyroptosis-related proteins were detected through quantitative reverse transcription PCR (RT-qPCR) and western blot. Additionally, the levels of CD4+T and CD8+T cells were assessed using flow cytometry. An aged rats hip fracture model was established to further investigate the impact of dexmedetomidine on postoperative mobility, cognition function, pyroptosis and immune cells in rats.
RESULTS: Postoperative cognitive function in patients did not show significant alteration when compared with pre-operation levels (p > 0.05). There were notable reduction in the levels of interleukin-18 (IL-18), Caspase-3, Gasdermin-D (GSDMD) and NLR Family Pyrin Domain Containing 3 (NLRP3) (p < 0.001), accompanied by an increase in the proportion of CD4+T cells and an decrease in CD8+T cells after operation (p < 0.01). In aged rats, postoperative exploratory activities increased compared to their preoperative state. Compared with preoperative levels, the levels of interleukin-1β (IL-1β), IL-18, Caspase-3, GSDMD, and NLRP3 were significantly decreased (p < 0.001), the proportion of CD4+T cells was increased, and the proportion of CD8+T cells was decreased postoperatively (p < 0.01).
CONCLUSIONS: Although there was no significant alteration in postoperative cognitive function in patients, dexmedetomidine may still play a role in mitigating POCD potentially due to its effects on reducing immune inflammation and pyroptosis markers. Further research is needed to fully understand the underlying mechanisms and its clinical implications.