虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响

摘要 目的：探讨虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响。方法：C57BL/6J雄性老年小鼠，18月龄，体重24~28 g，随机分为4组：假手术组（Sham组）、术后认知功能障碍组（POCD组）、低剂量虎杖苷组（PD1组）、高剂量虎杖苷组（PD2组）。Sham组老年小鼠仅接受水合氯醛麻醉，不行外科手术；POCD组老年小鼠接受腹部手术以制备POCD老年动物模型；PD1组小鼠制备POCD模型，并于术后即刻、24 h和48 h分别腹腔注射低剂量虎杖苷25 mg/kg；PD2组小鼠制备POCD模型，并于术后即刻、24 h和48 h分别腹腔注射高剂量虎杖苷50 mg/kg。使用Morris水迷宫行为学实验评估老年小鼠术后认知功能，使用Western blot法检测术后小鼠海马Nrf2、HO-1、HMGB1、Iba-1蛋白水平，检测海马活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）含量以反映术后海马氧化应激水平。结果：（1）与Sham组比较，POCD组老年小鼠术后逃离潜伏期显著增加（P<0.05），穿越平台次数和目标象限停留时间下降（P<0.05），海马Nrf2和HO-1蛋白表达水平明显降低（P<0.05），氧化应激产物ROS和MDA含量增加（P<0.05），抗氧化酶SOD活性降低（P<0.05），Iba-1和HMGB1蛋白表达水平增加（P<0.05）；（2）与POCD组比较，PD1组和PD2组小鼠术后逃离潜伏期缩短（P<0.05），穿越平台次数和目标象限停留时间增多（P<0.05），海马Nrf2和HO-1蛋白表达水平升高（P<0.05），ROS和MDA含量减少（P<0.05），SOD活性增加（P<0.05），Iba-1和HMGB1蛋白表达减少（P<0.05）。结论：虎杖苷可减轻老年小鼠术后认知功能损伤，缓解术后海马氧化应激和神经炎症，其机制可能与促进Nrf2/HO-1信号通路有关。

Effects of Polydatin on Postoperative Cognitive Dysfunction, Hippocampal Oxidative Stress and Neuroinflammation in Aged Mice

ABSTRACT Objective: To investigate the effect of polydatin treatment on postoperative cognitive dysfunction, hippocampal oxidative stress and neuroinflammation in aged mice. Methods: C57BL/6J male aged mice, 18 months old, weighing 24-28 g, were randomly divided into 4 groups: sham operation group (Sham group), postoperative cognitive dysfunction group (POCD group), low-dose polydatin group (PD1 group), high-dose polydatin group (PD2 group). The mice in the Sham group received only chloral hydrate anesthesia without surgery; the mice in the POCD group received abdominal surgery to prepare the POCD model; mice in PD1 group underwent abdominal surgery and received intraperitoneal injection of 25 mg/kg polydatin immediately, 24 h and 48 h after surgery; mice in PD2 group underwent abdominal surgery and received intraperitoneal injection of 50 mg/kg polydatin immediately, 24 h and 48 h after surgery. From postoperative day 5 to postoperative day 9, Morris water maze test was used to evaluate postoperative cognitive function. Western blot was used to determine the protein expression levels of Nrf2, HO-1, HMGB1, and Iba-1 in the hippocampus. The concentration of reactive oxygen species (ROS), malondialdehyde (MDA) as well as superoxide dismutase (SOD) in the hippocampus were detected to reflect the postoperative hippocampal oxidative stress level. Results: (1) Compared with the Sham group, the mice in the POCD group had a longer escape latency(P<0.05), decreased platform crossing times and time spent in the target quadrant(P<0.05), reduced expression levels of Nrf2 and HO-1 proteins (P<0.05), increased oxidative products ROS and MDA (P<0.05), decreased activity of antioxidant enzyme SOD (P<0.05), and elevated protein expression levels of Iba-1 and HMGB1(P<0.05); (2) Compared with POCD group, mice in PD1 group and PD2 group had shorter escape latency (P<0.05), increased platform crossing times and time spent in the target quadrant (P<0.05), elevated expression levels of Nrf2 and HO-1 proteins(P<0.05), reduced ROS and MDA(P<0.05), improved SOD activity(P<0.05), and decreased protein expression levels of Iba-1 and HMGB1 (P<0.05). Conclusion: Polydatin can alleviate postoperative cognitive impairment in aged mice, and reduce postoperative hippocampal oxidative stress and neuroinflammation. Its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.