Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice
Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice
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高同型半胱氨酸血症是老年小鼠 PND 易感性增加的关键
DOI：
10.1002/acn3.50838
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发表时间：
2019-07-29
影响因子：
5.3
通讯作者：
Xiong, Lize
中科院分区：
文献类型：
--
作者：
Zhao, Guangchao;Deng, Jiao;Xiong, Lize
背景：术后神经认知障碍（PND）是一种严重的术后并发症，目前尚无有效的治疗方法，影响高达19-52%的老年患者。年龄和手术类型已被确定为风险因素。然而，导致老年人风险增加的原因尚不清楚。方法我们利用老年小鼠的PND模型，在全身麻醉下进行实验性剖腹手术，以评估高同型半胱氨酸血症与PND易感性增加之间的因果关系。PND通过新颖物体任务、恐惧条件反射测试和巴恩斯迷宫测试进行评估。分别于术前、术后即刻及术后第1 ~ 29天采用ELISA法检测血清同型半胱氨酸（Hcy）、维生素B12和叶酸水平。还测试了包括饮食补充维生素B12 +叶酸（Vit B12 + FA）和S-腺苷甲硫氨酸（SAM）注射针对高同型半胱氨酸血症的预防策略的有效性。结果老年小鼠术后PND至少持续2周，而青年小鼠术后PND持续时间较短。血清同型半胱氨酸结果表明，术后认知能力和围手术期同型半胱氨酸水平显着相关。术前补充维生素B12和叶酸（FA）或注射S-腺苷蛋氨酸（SAM）可降低围手术期血清Hcy水平，抑制PND的发生。结论血清同型半胱氨酸水平升高是导致老年小鼠PND易感性增加的根本原因。术前饮食补充VitB 12 + FA可有效降低老年小鼠PND的发生率，是一种有前景的预防性治疗方法。
Background Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19-52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood. Methods We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S-adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested. Results PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S-adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice. Conclusions Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.