Citation: | CHEN Yan, GAO Xiaozeng. Mechanism of dexmedetomidine in improving early cognitive dysfunction in rats after hepatic lobectomy by regulating miR-182-5p/BDNF[J]. Journal of Clinical Medicine in Practice, 2024, 28(19): 48-54. DOI: 10.7619/jcmp.20241385 |
To investigate the effect of dexmedetomidine (DEX) on early cognitive dysfunction after hepatic lobectomy by regulating microRNA-182-5p/brain-derived neurotrophic factor (miR-182-5p/BDNF) axis in rats.
Sixty specific pathogen free(SPF) SD male rats were randomly divided into control group, model group, DEX low dose treatment group (25 μg/kg), DEX medium dose treatment group (50 μg/kg), DEX high dose treatment group (100 μg/kg), and DEX+ miR-182-5p mimic group, with 10 rats each group. The rats in the model group were anesthetized with sevoflurane and then underwent partial hepatectomy. The rats in DEX low-, medium-, and high-dose treatment groups were injected with DEX (25, 50, and 100 μg/kg) intraperitoneally and inhaled sevoflurane for 30 minutes before partial hepatectomy. DEX + miR-182-5p mimic group rats were treated with the same method as DEX high-dose treatment group, and miR-182-5p mimic (50 μg) was injected through tail vein every 2 days after operation. Rats in the control group were intraperitoneally injected with 2 mL/kg normal saline, then anesthetized by inhalation of sevoflurane for 2 hours. Morris water maze test and Neurological Severity Scale (NSS) were used to evaluate the postoperative cognitive function and neurological function damage of rats in each group. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the level of miR-182-5p in rat hippocampus. The protein expression level of BDNF in hippocampus was determined by western blot. The binding region of miR-182-5p and BDNF 3'UTR was analyzed by bioinformatics, and the targeting relationship between miR-182-5p and BDNF was detected by dual luciferase reporter gene assay.
The results showed that compared with the control group, the escape latency of Morris water maze test in the model group was significantly prolonged at 2 to 5 days after operation (P < 0.05), and the NSS scores in the model group were significantly increased at 1, 3 and 7 d after operation (P < 0.05). Compared with the model group, the rats in the DEX treatment group had significantly shorter escape latency of Morris water maze test at 2 to 5 days after operation, and significantly lower NSS scores at 3 and 7 days after operation in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had significantly prolonged escape latency of Morris water maze test at 2 to 5 days after operation, and significantly increased NSS scores at 3 and 7 days after operation (P < 0.05). Compared with the control group, the level of miR-182-5p in the hippocampus of the model group was significantly increased, and the level of BDNF was significantly decreased (P < 0.05). Compared with the model group, the DEX treatment group had a significant reduction in the level of miR-182-5p and a significant increase in the level of BDNF in the hippocampus after surgery in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had a significant increase in the level of miR-182-5p and a significant reduction in the level of BDNF (P < 0.05). The dual luciferase reporter gene assay verified the targeted binding of miR-182-5p to BDNF.
DEX improves early cognitive dysfunction in rats after hepatic lobectomy by inhibiting miR-182-5p and increasing BDNF levels.
[1] |
BOGOLEPOVA A N. Postoperative cognitive dysfunction[J]. Zh Nevrologii Ⅰ Psikhiatrii Imeni S S Korsakova, 2022, 122(8): 17-11.
|
[2] |
LIN X Y, CHEN Y R, ZHANG P, et al. The potential mechanism of postoperative cognitive dysfunction in older people[J]. Exp Gerontol, 2020, 130: 110791. doi: 10.1016/j.exger.2019.110791
|
[3] |
WEI P H, YANG F, ZHENG Q, et al. The potential role of the NLRP3 inflammasome activation as a link between mitochondria ROS generation and neuroinflammation in postoperative cognitive dysfunction[J]. Front Cell Neurosci, 2019, 13: 73.
|
[4] |
YANG Y, LIU Y, ZHU J X, et al. Neuroinflammation-mediated mitochondrial dysregulation involved in postoperative cognitive dysfunction[J]. Free Radic Biol Med, 2022, 178: 134-146. doi: 10.1016/j.freeradbiomed.2021.12.004
|
[5] |
HAN X, CHENG X L, XU J Y, et al. Activation of TREM2 attenuates neuroinflammation via PI3K/Akt signaling pathway to improve postoperative cognitive dysfunction in mice[J]. Neuropharmacology, 2022, 219: 109231. doi: 10.1016/j.neuropharm.2022.109231
|
[6] |
ZENG K, LONG J Y, LI Y, et al. Preventing postoperative cognitive dysfunction using anesthetic drugs in elderly patients undergoing noncardiac surgery: a systematic review and meta-analysis[J]. Int J Surg, 2023, 109(1): 21-31. doi: 10.1097/JS9.0000000000000001
|
[7] |
TASBIHGOU S R, BARENDS C R M, ABSALOM A R. The role of dexmedetomidine in neurosurgery[J]. Best Pract Res Clin Anaesthesiol, 2021, 35(2): 221-229. doi: 10.1016/j.bpa.2020.10.002
|
[8] |
KAYE A D, CHERNOBYLSKY D J, THAKUR P, et al. Dexmedetomidine in enhanced recovery after surgery (ERAS) protocols for postoperative pain[J]. Curr Pain Headache Rep, 2020, 24(5): 21. doi: 10.1007/s11916-020-00853-z
|
[9] |
XIE X L, SHEN Z W, HU C W, et al. Dexmedetomidine ameliorates postoperative cognitive dysfunction in aged mice[J]. Neurochem Res, 2021, 46(9): 2415-2426. doi: 10.1007/s11064-021-03386-y
|
[10] |
YAZIT N A A, JULIANA N, DAS S, et al. Association of micro RNA and postoperative cognitive dysfunction: a review[J]. Mini Rev Med Chem, 2020, 20(17): 1781-1790. doi: 10.2174/1389557520666200621182717
|
[11] |
SHU L Z, LI X Y, LIU Z L, et al. Bile exosomal miR-182/183-5p increases cholangiocarcinoma stemness and progression by targeting HPGD and increasing PGE2 generation[J]. Hepatology, 2024, 79(2): 307-322. doi: 10.1097/HEP.0000000000000437
|
[12] |
沈晓莉, 庄雪明, 钱梦书, 等. 微小RNA-182-5p通过靶向MAPK1调控MAPK/NF-κB通路治疗急性肺损伤的研究[J]. 实用临床医药杂志, 2022, 26(5): 79-85. doi: 10.7619/jcmp.20214224
|
[13] |
XIAO T, MENG W, JIN Z L, et al. MiR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration[J]. Commun Biol, 2022, 5(1): 771. doi: 10.1038/s42003-022-03714-0
|
[14] |
LIMA GIACOBBO B, DOORDUIN J, KLEIN H C, et al. Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation[J]. Mol Neurobiol, 2019, 56(5): 3295-3312. doi: 10.1007/s12035-018-1283-6
|
[15] |
LIN C C, HUANG T L. Brain-derived neurotrophic factor and mental disorders[J]. Biomed J, 2020, 43(2): 134-142. doi: 10.1016/j.bj.2020.01.001
|
[16] |
GAO L N, ZHANG Y, STERLING K, et al. Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential[J]. Transl Neurodegener, 2022, 11(1): 4. doi: 10.1186/s40035-022-00279-0
|
[17] |
DI CARLO P, PUNZI G, URSINI G. Brain-derived neurotrophic factor and schizophrenia[J]. Psychiatr Genet, 2019, 29(5): 200-210. doi: 10.1097/YPG.0000000000000237
|
[18] |
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals[M]. 8th ed. Washington (DC): National Academies Press (US), 2011: 21-53.
|
[19] |
宋丹丹, 陈雨涵, 罗一, 等. 银杏叶提取物对老年大鼠肝叶部分切除术后认知功能障碍及大脑海马CA3区凋亡影响[J]. 临床和实验医学杂志, 2018, 17(21): 2265-2268.
|
[20] |
张臣, 蔡灵乐, 李浩田, 等. 右美托咪定对老年大鼠阑尾切除术术后认知功能障碍的影响及其机制[J]. 中国老年学杂志, 2023, 43(2): 406-410.
|
[21] |
程亮亮, 田毅, 谭义文, 等. 右美托咪定通过PI3K/Akt/mTOR信号通路对肝叶切除术后神经认知功能障碍大鼠海马神经元自噬的影响[J]. 西部医学, 2021, 33(6): 793-798, 803.
|
[22] |
RUMP K, ADAMZIK M. Epigenetic mechanisms of postoperative cognitive impairment induced by anesthesia and neuroinflammation[J]. Cells, 2022, 11(19): 2954. doi: 10.3390/cells11192954
|
[23] |
HUA M M, MIN J. Postoperative cognitive dysfunction and the protective effects of enriched environment: a systematic review[J]. Neurodegener Dis, 2020, 20(4): 113-122. doi: 10.1159/000513196
|
[24] |
WU W F, LIN J T, QIU Y K, et al. The role of epigenetic modification in postoperative cognitive dysfunction[J]. Ageing Res Rev, 2023, 89: 101983. doi: 10.1016/j.arr.2023.101983
|
[25] |
INGUSTU D G, PAVEL B, PALTINEANU S I, et al. The management of postoperative cognitive dysfunction in cirrhotic patients: an overview of the literature[J]. Medicina, 2023, 59(3): 465. doi: 10.3390/medicina59030465
|
[26] |
PENG W Y, LU W, JIANG X F, et al. Current progress on neuroinflammation-mediated postoperative cognitive dysfunction: an update[J]. Curr Mol Med, 2023, 23(10): 1077-1086. doi: 10.2174/1566524023666221118140523
|
[27] |
MOMENI M, KHALIFA C, LEMAIRE G, et al. Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery[J]. Br J Anaesth, 2021, 126(3): 665-673. doi: 10.1016/j.bja.2020.10.041
|
[28] |
XIAO M, JIANG C F, GAO Q, et al. Effect of dexmedetomidine on cardiac surgery patients[J]. J Cardiovasc Pharmacol, 2023, 81(2): 104-113. doi: 10.1097/FJC.0000000000001384
|
[29] |
GOVÊIA C S, MIRANDA D B, OLIVEIRA L V B, et al. Dexmedetomidine reduces postoperative cognitive and behavioral dysfunction in adults submitted to general anesthesia for non-cardiac surgery: meta-analysis of randomized clinical trials[J]. Braz J Anesthesiol, 2021, 71(4): 413-420.
|
[30] |
YU H, KANG H, FAN J X, et al. Influence of dexmedetomidine on postoperative cognitive dysfunction in the elderly: a meta-analysis of randomized controlled trials[J]. Brain Behav, 2022, 12(8): e2665. doi: 10.1002/brb3.2665
|
[31] |
WEI F S, RAO M W, HUANG Y L, et al. MiR-182-5p delivered by plasma exosomes promotes sevoflurane-induced neuroinflammation and cognitive dysfunction in aged rats with postoperative cognitive dysfunction by targeting brain-derived neurotrophic factor and activating NF-κB pathway[J]. Neurotox Res, 2022, 40(6): 1902-1912. doi: 10.1007/s12640-022-00597-1
|