Original Article

Intervention of NF-Κb Signaling Pathway and Preventing Post-Operative Cognitive Dysfunction as Well as Neuronal Apoptosis

Abstract

Background: The Postoperative cognitive dysfunction (POCD) model was constructed by resection of the left hepatic lobe in aged mice to determine the behavioral effects of the POCD model in aged mice and the relationship between NF-κB and POCD in apoptosis and autophagy. Provide a theoretical basis for POCD prevention and treatment.

Methods: This study was carried out in Ningbo No. 6 Hospital, Zhejiang, China, from Jun 2019 to Dec 2020. The POCD model was constructed after resection of the left extrahepatic lobe in aged mice and randomly divided into 6 groups: sham operation group, operation group (normal saline control group, solvent group, YC-1 group, PDTC group and 3-MA group). Related indicators of behavioral changes, neuronal inflammatory responses, apoptosis, and autophagy were examined.

Results: The escape latency of the aged mice in the surgical group was significantly prolonged at three time points compared with the control group, and the number of insertions decreased significantly. Microglia are activated and the inflammatory response is increased, whereas PDTC has an inhibitory effect. It was demonstrated that apoptosis and necrosis of neurons can be induced by the NF-κb pathway, and autophagy can be promoted, whereas autophagy occurs before apoptosis.

Conclusion: Activation of NF-κb pathway in neurons after POCD causes neuronal apoptosis and autophagy, and cognitive impairment occurs. PDTC, a NF-κb pathway inhibitor, can effectively reduce neuronal apoptosis induced by secondary brain injury after POCD. Necrosis, to protect the brain tissue.

1. Tian Y, Guo S, Zhang Y, Xu Y, Zhao P, Zhao X (2017). Effects of hydrogen-rich saline on hepatectomy-induced postoper-ative cognitive dysfunction in old mice. Mol Neurobiol, 54(4):2579-2584.
2. Jiang P, Ling Q, Liu H, Tu W (2015). In-tracisternal administration of an interleu-kin-6 receptor antagonist attenuates sur-gery-induced cognitive impairment by in-hibition of neuroinflammatory responses in aged rats. Exp Ther Med, 9(3):982-986.
3. Ding Y, Shi C, Chen L, et al (2017). Effects of andrographolide on postoperative cognitive dysfunction and the association with nf?κb/mapk pathway. Oncol Lett, 14(6):7367-7373.
4. Zheng JW, Meng B, Li XY, et al (2017). Nf-κb/p65 signaling pathway: a potential therapeutic target in postoperative cogni-tive dysfunction after sevoflurane anestesia. Eur Rev Med Pharmacol Sci, 21(2):394-407.
5. Yu L, Sun L, Chen S (2014). Protective ef-fect of senegenin on splenecto-my?induced postoperative cognitive dys-function in elderly rats. Exp Ther Med, 7(4):821-826.
6. Li Z, Cao Y, Li L, et al (2014). Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dys-function. Biochem Biophys Res Commun, 449(1):74-80.
7. Cao Y, Li Z, Ma L, et al (2018). Isoflu-rane?induced postoperative cognitive dysfunction is mediated by hypox-ia?inducible factor?1α?dependent neu-roinflammation in aged rats. Mol Med Rep, 17(6):7730-7736.
8. Yang N, Liang Y, Yang P, Wang W, Zhang X, Wang J (2016). Tnf-α receptor antag-onist attenuates isoflurane-induced cogni-tive impairment in aged rats. Exp Ther Med, 12(1):463-468.
9. Raju M (2018). Population Ageing and the Elderly. Indian J Psychiatry, 60(Suppl 3):S295.
10. Chen C, Zhang Z, Chen T, Peng M, Xu X, Wang Y (2015). Prolonged mechanical ventilation–induced neuroinflammation affects postoperative memory dysfunc-tion in surgical mice. Crit Care, 19(1):159.
11. Yu JJ, Zhu LX, Zhang J, et al (2017). Activa-tion of nf-κb-autophagy axis by 2-hydroxyethyl methacrylate commits den-tal mesenchymal cells to apoptosis. Toxi-col Sci, 157(1):100-111.
12. Zhu X, Huang L, Gong J, et al (2017). Nf-κb pathway link with er stress-induced autophagy and apoptosis in cervical tu-mor cells. Cell Death Discov, 3:17059.
13. Benjamin B, Perkins N D (2010). The skp2 promoter integrates signaling through the nf-κb, p53, and akt/gsk3β pathways to regulate autophagy and apoptosis. Mol Cell, 38(4):524-38.
14. Razgonova MP, Veselov VV, Zakharenko AM, et al (2019). Panax ginseng compo-nents and the pathogenesis of Alzhei-mer's disease (Review). Mol Med Rep, 19(4):2975-2998.
15. Su J, Liu F, Xia M,et al (2015). P62 partici-pates in the inhibition of nf-κb signaling and apoptosis induced by sulfasalazine in human glioma u251 cells. Oncol Rep, 34(1):235-43.
16. Tang MM, Lin WJ, Pan YQ, Li YC (2018). Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression. Front Cell Neurosci, 12:255.
17. Friess L, Cheray M, Keane L, Grabert K, Joseph B (2021). Atg7 deficiency in mi-croglia drives an altered transcriptomic profile associated with an impaired neu-roinflammatory response. Mol Brain, 14(1):87.
18. Huang Z, Zhou T, Sun X, et al (2018). Necroptosis in microglia contributes to neuroinflammation and retinal degenera-tion through TLR4 activation. Cell Death Differ, 25(1):180-189.
19. Liwei W, Qinghui Z, Weiqi D, et al (2017). Quercetin pretreatment attenuates hepatic ischemia reperfusion-induced apoptosis and autophagy by inhibiting erk/nf-\r, κ\r, b pathway. Gastroenterol Res Pract, 2017:9724217.
20. Zhu BS, Xing CG, Lin F, et al (2011). Block-ing nf-κb nuclear translocation leads to p53-related autophagy activation and cell apoptosis. World J Gastroenterol, 17(4):478-87.
21. Shen X, Ma L, Dong W,et al (2016). Au-tophagy regulates intracerebral hemor-rhage induced neural damage via apopto-sis and nf-κb pathway. Neurochem Int, 96:100-12.
22. Salminen A, Hyttinen JM, Kauppinen A, Kaarniranta K (2012). Context-dependent regulation of autophagy by ikk-nf-κb sig-naling: impact on the aging process. Int J Cell Biol, 2012:849541.
23. Tang DL, Cui HF, Yu S, Lin T, Liu ZH, Zhang HM (2015). Effects of tanyu tongzhi formula on nf-κb pathway, au-tophagy and antiapoptosis of rats with myocardial ischemia-reperfusion injury. Chinese Journal of Information on Traditional Chinese Medicine.
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IssueVol 51 No 1 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v51i1.8303
Keywords
Postoperative cognitive dysfunction (POCD) Neuronal apoptosis Autophagy
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How to Cite
1.
Yuan N, Wang X, Zhang Y, Kong L, Yuan L, Ge Y. Intervention of NF-Κb Signaling Pathway and Preventing Post-Operative Cognitive Dysfunction as Well as Neuronal Apoptosis. Iran J Public Health. 2022;51(1):124-132.