Objective To explore the effect of celecoxib on neural function in rats with acute intracerebral hemorrhage.
Methods SD rats were randomly divided into sham group, model group, inhibitor group and celecoxib group. Except the sham operation group, the cerebral hemorrhage model was made by autologous blood injection in each group. Rats in the inhibitor group were injected with extra cellular regulated protein kinase (ERK) inhibitor (DCZ19931) into the anterior ventricle on the basis of the model group. Celecoxib group rats were injected intraperitoneally with 100 mg·kg-1·d-1 celecoxib, for 2 weeks. The degree of neurological injury in rats was compared by Longa five-grade score. The water content of brain tissue of rats in each group was detected and the expression of aquaporin 4 (AQP4) in brain tissue of rats in each group was detected by Western blotting. Enzyme-linked immunosorbent assay was used to detect the content of interleukin-1 (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malonaldehyde (MDA) in the brain tissue of rats in each group. Western blotting was used to detect the expression of mitogen-activated protein kinase (MAPK)/ERK signal pathway protein in rats of each group.
Result Compared with sham group, the neurological function score, brain water content, relative expression level of AQP4 protein, content of IL-1β, TNF-α and MDA, relative expression levels of p-ERK1 protein, p-ERK2 protein and MAPK protein in model group were significantly increased, while content of SOD was significantly decreased (P<0.05). Compared with model group, the neurological function score, brain water content, relative expression level of AQP4 protein, content of IL-1β, TNF-α and MDA, relative expression levels of p-ERK1 protein, p-ERK2 protein and MAPK protein in inhibitor group and celecoxib group were significantly decreased, while content of SOD was significantly increased (P<0.05).
Conclusion Celecoxib can effectively improve the neurological function of rats with acute intracerebral hemorrhage, and its mechanism may be related to the regulation of MAPK/ERK signal pathway and inhibition of inflammation.
1.Richards O, Cromie KJ, Akhunbay-Fudge C, et al. ABO blood group in aneurysmal subarachnoid haemorrhage-a pilot study[J]. Acta Neurochir (Wien), 2022, 164(2): 507-515. DOI: 10.1007/s00701-021-05079-5.
2.Solar P, Hendrych M, Barak M, et al. Blood-brain barrier alterations and edema formation in different brain mass lesions[J]. Front Cell Neurosci, 2022, 15(16): 922181. DOI: 10.3389/fncel.2022.922181.
3.Zhang J, Zhang X, Shang Y, et al. Effect of cinepazide maleate on serum inflammatory factors of ICU patients with severe cerebral hemorrhage after surgery[J]. Evid Based Complement Alternat Med, 2021, 5(28): 6562140. DOI: 10.1155/2021/6562140.
4.Jadaun KS, Mehan S, Sharma A, et al. Neuro protective effect of chrysophanol as a PI3K/AKT/mTOR signaling inhibitor in an experimental model of autologous blood-induced intracerebral hemorrhage[J]. Contem Med Sci, 2022, 5(2): 42. DOI: 10.1007/s11596-022-2496-x.
5.Bu X, Xia W, Wang X, et al. Butylphthalide inhibits nerve cell apoptosis in cerebral infarction rats via the JNK/p38 MAPK signaling pathway[J]. Exp ther med, 2021, 21(6): 28-30. DOI: 10.3892/etm.2021.9997.
6.Miao Y, Niu D, Wang Z, et al. Methylsulfonylmethane ameliorates inflammation via NF-κB and ERK/JNK-MAPK signaling pathway in chicken trachea and HD11 cells during mycoplasma gallisepticum infection[J]. Poult Sci, 2022, 101(4): 101706. DOI: 10.1016/j.psj.2022. 101706.
7.张浩, 权天龙. 塞来昔布对脑出血模型大鼠TLR4/NF-κB信号通路及GLT-1表达的影响[J].中西医结合心脑血管病杂志, 2021, 19(4): 5-10. [Zhang H, Quan TL. Effects of celecoxib on TLR4/NF-B signaling pathway and GLT-1 in rats with intracerebral hemorrhage[J]. Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, 2021, 19(4): 5-10.] DOI: 10.12102/j.issn.1672-1349.2021.04.010.
8.Chen QX, Yu TT, Zhang Y, et al. Effect of acupuncture on cerebral hematoma volume and HO-1 expression in rats with acute cerebral hemorrhage[J]. TMR, 2021, 8(7): 1-6. DOI: 10.12032/TMRIM202105007.
9.周经霞, 陈琳, 陈擘璨, 等. 血管内皮生长因子通过PI3K-Akt和MAPK-ERK通路促进脑梗死大鼠血管新生机制[J].中国老年学杂志, 2019, 39(15): 4-8. [Zhou JX, Chen L, Chen BC, et al. The mechanism by which vascular endothelial growth factor promotes angiogenesis in rats with cerebral infarction through the PI3K-Akt and MAPK-ERK pathways[J]. Chinese Journal of Gerontology, 2019, 39(15): 4-8.] DOI: 10.3969/j.issn.1005-9202. 2019.15.047.
10.Wei F, Cui Y, Guo X, et al. Correlations of inflammatory factors, CCCK-18, MMP-9 and D-dimer with APACHE II score and prognosis of patients with acute cerebral hemorrhage[J]. Minerva Med, 2020, 20(5): 25-30. DOI: 10. 23736/S0026-4806.20.06685-9.
11.Lu S, Li J, Cheng F. The effect of electroacupuncture on the pathology and ultrastructure of brain tissue around hematoma in rats with cerebral hemorrhage[J]. Acta Microscopica, 2020, 29(5): 2675-2682. https://pubmed.ncbi.nlm.gov/35470409/.
12.Cook AM, Morgan JG, Hawryluk GWJ, et al. Guidelines for the acute treatment of cerebral edema in neurocritical care patients[J]. Neurocrit Care, 2020, 32(3): 647-666. DOI: 10.1007/s12028-020-00959-7.
13.Lin YW, Yeh SJ, Tang SC, et al. Improvement after celecoxib treatment in patients with thalamic hemorrhage-a case report[J]. Acta Neurol Taiwan, 2022, 31(4): 84-89. https://pubmed.ncbi.nlm.nih.gov/35470409/.
14.Kirshner H, Schrag M. Management of intracerebral hemorrhage: update and future therapies[J]. Curr Neurol Neurosci Rep, 2021, 21(10): 57-60. DOI: 10.1007/s11910-021-01144-9.
15.Li N, Ying Y, Yang B. Aquaporins in edema[J]. Adv Exp Med Biol, 2023, 1398: 281-287. DOI: 10.1007/978-981-19-7415-1_19.
16.Chen S, Peng J, Sherchan P, et al. TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K/Akt pathway after intracerebral hemorrhage in mice[J]. J Neuroinflammation, 2020, 17(1): 168-178. DOI: 10.1186/s12974-020-01853-x.
17.Liu X, Wu G, Tang N, et al. Glymphatic drainage blocking aggravates brain edema, neuroinflammation via modulating TNF-α, IL-10, and AQP4 after intracerebral hemorrhage in rats[J]. Front Cell Neurosci, 2021, 17(15): 784154. DOI: 10.3389/fncel.2021.784154.
18.Song D, Yeh CT, Wang J, et al. Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage[J]. Front Immunol, 2022, 5(13): 989503. DOI: 10.3389/fimmu. 2022.989503.
19.Tang J, Yan B, Tang Y, et al. Baicalein ameliorates oxidative stress and brain injury after intracerebral hemorrhage by activating the Nrf2/ARE pathway via miR-106a-5p/PHLPP2 axis[J]. Int J Neurosci, 2023, 133(12): 1380-1393. DOI: 10.1080/00207454.2022.2080676.
20.Wang F, Li WL, Shen LJ. Crocin alleviates intracerebral hemorrhage-induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation[J]. Neurotox Res, 2022, 40(2): 596-604. DOI: 10.1007/s12640-022- 00500-y.
21.Li C, Zhu L, Dai Y, et al. Diet-induced high serum levels of trimethylamine-N-oxide enhance the cellular inflammatory response without exacerbating acute intracerebral hemorrhage injury in mice[J]. Oxid Med Cell Longev, 2022, 2022: 1599747. DOI: 10.1155/2022/1599747.
22.Cao S, Wei J, Cai Y, et al. Network pharmacology prediction and experimental verification for anti-ferroptosis of edaravone after experimental intracerebral hemorrhage[J]. Mol Neurobiol, 2023, 11(5): 25-30. DOI: 10.1007/s12035-023-03279-x.