Wen Cen, Xie Tao, Pan Ke, Deng Yu, Zhao Zhijia, Li Na, Bian Jinjun, Deng Xiaoming, Zha Yanping
Faculty of Anesthesiology, Changhai Hospital, Navy Medical University, Shanghai 200433, China.
Aging (Albany NY). 2020 Feb 26;12(4):3862-3879. doi: 10.18632/aging.102856.
Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotomy model with isoflurane anesthesia to study the effects of acetate on perioperative neurocognitive disorders in aged mice. Neurocognitive function was assessed with open-field tests and Morris water maze tests 3 or 7 days post-surgery. Acetate ameliorated the surgery-induced cognitive deficits of aged mice and inhibited the activation of IBA-1, a marker of microglial activity. Acetate also reduced expression of inflammatory proteins (tumor necrosis factor-α, interleukin-1β and interleukin-6), oxidative stress factors (NADPH oxidase 2, inducible nitric oxide synthase and reactive oxygen species), and signaling molecules (nuclear factor kappa B and mitogen-activated protein kinase) in the hippocampus. BV2 microglial cells were used to verify the anti-inflammatory effects of acetate . Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when GPR43 was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits. This makes acetate is a promising therapeutic for surgery-induced neurocognitive disorders and neuroinflammation.
围手术期神经认知障碍在接受外科手术的老年患者中很常见。小胶质细胞激活诱导的神经炎症是这些神经障碍的一个标志。在炎症性疾病的背景下，醋酸盐可以抑制炎症。我们采用异氟烷麻醉的剖腹探查模型来研究醋酸盐对老年小鼠围手术期神经认知障碍的影响。在手术后3天或7天，通过旷场试验和莫里斯水迷宫试验评估神经认知功能。醋酸盐改善了老年小鼠手术诱导的认知缺陷，并抑制了小胶质细胞活性标志物IBA-1的激活。醋酸盐还降低了海马中炎症蛋白（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）、氧化应激因子（NADPH氧化酶2、诱导型一氧化氮合酶和活性氧）以及信号分子（核因子κB和丝裂原活化蛋白激酶）的表达。使用BV2小胶质细胞来验证醋酸盐的抗炎作用。醋酸盐抑制了脂多糖处理的BV2小胶质细胞中的炎症，但在GPR43沉默时则没有。这些结果表明，醋酸盐可能与GPR43结合，从而抑制小胶质细胞活性，抑制神经炎症，并预防记忆缺陷。这使得醋酸盐成为手术诱导的神经认知障碍和神经炎症的一种有前景的治疗方法。
