PDF(670 KB)
尿石素A对小鼠异氟醚麻醉所致术后认知功能障碍的改善作用及其机制
许敏慧, 程晓雷, 许继岩, 江林昊, 夏天娇
PDF(670 KB)
PDF(670 KB)
尿石素A对小鼠异氟醚麻醉所致术后认知功能障碍的改善作用及其机制
)Effect of urolithin A on postoperative cognitive dysfunction induced by isoflurane anesthesia in mice and its mechanism
)目的 探讨尿石素A（UA）对长时程异氟醚麻醉所致小鼠术后认知功能障碍（POCD）的改善作用，并阐明其可能的作用机制。 方法 24只健康雄性C57BL/6小鼠随机分为空白对照组、麻醉组和UA组，每组8只。UA组小鼠于麻醉前2 d每天腹腔注射200 μL UA溶液，空白对照组和麻醉组小鼠给予等体积生理盐水，麻醉组和UA组小鼠制备长时程异氟醚麻醉模型，空白对照组小鼠不作处理。采用Y迷宫实验检测各组小鼠轮替正确率、移动距离和移动速度，条件恐惧实验检测各组小鼠僵直时间百分率，Western blotting法检测各组小鼠海马组织中白细胞介素（IL）-1β、IL-10和成熟脑源性神经营养因子（mBDNF）蛋白表达水平。 结果 Y迷宫实验，与空白对照组比较，麻醉组小鼠轮替正确率明显降低（P<0.01）；与麻醉组比较，UA组小鼠轮替正确率明显升高（P<0.01）。条件恐惧实验中情境记忆测试，与空白对照组比较，麻醉组小鼠僵直时间百分率明显降低（P<0.01）；与麻醉组比较，UA组小鼠僵直时间百分率明显升高（P<0.05）；线索记忆测试，各组小鼠僵直时间百分率比较差异无统计学意义（P>0.05）。Western blotting法，与空白对照组比较，麻醉组小鼠海马组织中IL-1β蛋白表达水平明显升高（P<0.01），IL-10和mBDNF蛋白表达水平明显降低（P<0.01）；与麻醉组比较，UA组小鼠海马组织中IL-1β蛋白表达水平明显降低（P<0.05），IL-10和mBDNF蛋白表达水平明显升高（P<0.05或P<0.01）。 结论 UA可以改善小鼠的POCD，其作用机制可能与UA的抗炎活性可抑制POCD小鼠的中枢炎症且上调mBDNF蛋白表达有关。
Objective To discuss the improvement effect of uric acid （UA） on the postoperative cognitive dysfunction （POCD） in the mice anesthetized with isoflurane for a long duration， and to clarify its possible mechanism. Methods Twenty-four healthy male C57BL/6 mice were randomly divided into blank control group，anesthesia group， and UA group, and there were eight mice in each group. The mice in UA group were injected intraperitoneally with 200 μL UA solution daily for 2 d before anesthesia. The mice in blank control group and anesthesia group were given the same volume of saline; the mice in anesthesia group and UA group were used to prepare the models of long-duration isoflurane anesthesia， while the mice in blank control group were untreated. Y-maze tests was used to detect the alternation success rate， movement distances， and movement speeds of the mice in various groups； situational fear experiment was used to detect the percentages of freezing time； Western blotting method was used to detect the expression levels of interleukin (IL)-1β， IL-10， and mature brain-derived neurotrophic factor (mBDNF) proteins in hippocampus tissue of the mice in various groups. Results The Y-maze test results showed that compared with blank control group， the alternation success rate of the mice in anesthesia group was significantly decreased (P<0.01)； compared with anesthesia group， the alternation success rate of the mice in UA group was significantly increased (P<0.01). The situational fear experiment results showed that compared with blank control group, the percentage of freezing time of the mice in anesthesia group was significantly decreased (P<0.01)； compared with anesthesia group， the percentage of freezing time of the mice in UA group was significantly increased (P<0.05). The cued memory experiment resutls showed that there were no significant differences of the percentage of freezing time of the mice between various groups (P>0.05). The Western blotting results showed that compared with blank control group， the expression level of IL-1β protein in hippocampus tissue of the mice in anesthesia group was increased (P<0.01)， while the expression levels of IL-10 and mBDNF proteins were decreased (P<0.01)； compared with anesthesia group, the expression level of IL-1β protein in hippocampus tissue of the mice in UA group was decreased (P<0.05), and the expression levels of IL-10 and mBDNF proteins were increased (P<0.05 or P<0.01). Conclusion UA can improve the POCD in the mice, and its mechnasim may be related with its anti-inflammatory activity inhibiting the central inflammation and upregulating the mBDNF protein expression.
尿石素A / 异氟醚 / 术后认知功能障碍 / 白细胞介素 / 脑源性神经营养因子
Urolithin A / Isoflurane / Postoperative cognitive dysfunction / Interleukin / Brain-derived neurotrophic factor
R742
| 1 | ING C， HEGARTY M K， PERKINS J W， et al. Duration of general anaesthetic exposure in early childhood and long-term language and cognitive ability［J］. Br J Anaesth， 2017， 119（3）： 532-540. |
| 2 | VUTSKITS L， XIE Z C. Lasting impact of general anaesthesia on the brain： mechanisms and relevance［J］. Nat Rev Neurosci， 2016， 17（11）： 705-717. |
| 3 | JIANG S， MIAO B， CHEN Y. Prolonged duration of isoflurane anesthesia impairs spatial recognition memory through the activation of JNK1/2 in the hippocampus of mice［J］. Neuroreport， 2017， 28（7）： 386-390. |
| 4 | ZUO C L， WANG C M， LIU J， et al. Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment［J］. CNS Neurosci Ther， 2018， 24（3）： 212-221. |
| 5 | GONG Z， HUANG J Y， XU B， et al. Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice［J］. J Neuroinflammation， 2019， 16（1）： 62. |
| 6 | LIN X H， YE X J， LI Q F， et al. Urolithin A prevents focal cerebral ischemic injury via attenuating apoptosis and neuroinflammation in mice［J］. Neuroscience， 2020， 448： 94-106. |
| 7 | FANG E F， HOU Y J， PALIKARAS K， et al. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease［J］. Nat Neurosci， 2019， 22（3）： 401-412. |
| 8 | BALLESTEROS-áLVAREZ J， NGUYEN W， SIVAPATHAM R， et al. Urolithin A reduces amyloid-beta load and improves cognitive deficits uncorrelated with plaque burden in a mouse model of Alzheimer’s disease［J］. Geroscience， 2023， 45（2）： 1095-1113. |
| 9 | TICINESI A， MANCABELLI L， CARNEVALI L， et al. Interaction between diet and microbiota in the pathophysiology of Alzheimer’s disease： focus on polyphenols and dietary fibers［J］. J Alzheimers Dis， 2022， 86（3）： 961-982. |
| 10 | GORJI N， MOEINI R， MEMARIANI Z.Almond， hazelnut and walnut， three nuts for neuroprotection in Alzheimer’s disease： a neuropharmacological review of their bioactive constituents［J］. Pharmacol Res， 2018， 129： 115-127. |
| 11 | XIAO Y， LI K L， BIAN J， et al. Urolithin A attenuates diabetes-associated cognitive impairment by ameliorating intestinal barrier dysfunction via N-glycan biosynthesis pathway［J］. Mol Nutr Food Res， 2022， 66（9）： e2100863. |
| 12 | QIU J R， CHEN Y， ZHUO J， et al. Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson’s disease model［J］. Neuropharmacology， 2022， 207： 108963. |
| 13 | GONZáLEZ-SARRíAS A， Nú?EZ-SáNCHEZ M á， TOMáS-BARBERáN F A， et al. Neuroprotective effects of bioavailable polyphenol-derived metabolites against oxidative stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells［J］. J Agric Food Chem， 2017， 65（4）： 752-758. |
| 14 | XU J L， YUAN C H， WANG G H， et al. Urolithins attenuate LPS-induced neuroinflammation in BV2Microglia via MAPK， Akt， and NF-κB signaling pathways［J］. J Agric Food Chem， 2018， 66（3）： 571-580. |
| 15 | BOAKYE Y D， GROYER L， HEISS E H. An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages［J］. Biochim Biophys Acta Gen Subj， 2018， 1862（1）： 61-70. |
| 16 | PIWOWARSKI J P， GRANICA S， ZWIERZY?SKA M， et al. Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials［J］. J Ethnopharmacol， 2014， 155（1）： 801-809. |
| 17 | PIWOWARSKI J P， KISS A K， GRANICA S， et al. Urolithins， gut microbiota-derived metabolites of ellagitannins， inhibit LPS-induced inflammation in RAW 264.7 murine macrophages［J］. Mol Nutr Food Res， 2015， 59（11）： 2168-2177. |
| 18 | COLUCCI-D’AMATO L， SPERANZA L， VOLPICELLI F. Neurotrophic factor BDNF， physiological functions and therapeutic potential in depression， neurodegeneration and brain cancer［J］. Int J Mol Sci， 2020， 21（20）： 7777. |
| 19 | WANG M Y， XIE Y H， QIN D D. Proteolytic cleavage of proBDNF to mBDNF in neuropsychiatric and neurodegenerative diseases［J］. Brain Res Bull， 2021， 166： 172-184. |
| 20 | LEAL G， BRAMHAM C R， DUARTE C B. BDNF and hippocampal synaptic plasticity［J］. Vitam Horm， 2017， 104： 153-195. |
/
| 〈 |
|
〉 |
AI Summary
