Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats

GAO Sai-hong ZHANG Xiao-liang YANG Ying-chun QIAO Hai-bing

Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (1) : 50-55.

PDF(9812 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(9812 KB)
Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (1) : 50-55. DOI: 10.16098/j.issn.0529-1356.2023.01.007
Neurobiology

Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats

  • GAO  Sai-hong  ZHANG Xiao-liang  YANG  Ying-chun  QIAO  Hai-bing*
Author information +
History +

Abstract

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury.   Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry.   Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0.05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0.05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant.   Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

Key words

Hyperlipidemia / Cerebral ischemia-reperfusion / Phosphorylated-p38 mitogen activated protein kinase / Bcl-2 assaciated X protein / B-cell lymphoma-2 / SB203580 / Immunohistochemistry / Rat  

Cite this article

Download Citations
GAO Sai-hong ZHANG Xiao-liang YANG Ying-chun QIAO Hai-bing. Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats[J]. Acta Anatomica Sinica. 2023, 54(1): 50-55 https://doi.org/10.16098/j.issn.0529-1356.2023.01.007

References

[1]Zhen YL, Ding CJ, Sun JQ, et al. Activation of the calcium-sensing receptor promotes apoptosis by modulating the JNK/p38 MAPK pathway in focal cerebral ischemia-reperfusion in mice[J]. Am J Transl Res, 2016, 8(2):911-921.
[2]Sheth KN, Smith EE, Grau-Sepulveda MV, et al. Drip and ship thrombolytic therapy for acute ischemic stroke: use, temporaltrends, andoutcomes[J]. Stroke, 2015, 46(3):732-739.
[3]Yin XY, Guo ShK, Tan J, et al. Effcts of adenosine preconditioning on the expression of tumor necrosis factor α and nuclear factor κB in rats after cerebral ischemia-reperfusion injury[J]. Acta Anatomica Sinica, 2020, 51(6):839-847. (in Chinese)
阴雪妍, 郭哨恺, 谭军, 等. 腺苷预处理对大鼠脑缺血-再灌注损伤后脑内肿瘤坏死因子α和核因子κB表达的影响[J]. 解剖学报, 2020, 51(6):839-847.
[4]Zechariah A, ElAli A, Hagemann N, et al. Hyperlipidemia attenuates vascular endothelial growth factor-induced angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via decreased pericyte coverage of brain endothelial cells[J]. Arterioscler Thromb Vasc Biol,2013, 33(7):1561-1567.
[5]Cao XL, Du J, Zhang Y, et al. Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats[J]. Exp Brain Res, 2015, 233(10):2753-2765.
[6]Schiavoni VS, Silva JPD, Lizarte Neto FS, et al.Morphologicaland immunohistochemical analysis of proteins CASPASE 3 and XIAP in rats subjected to cerebral ischemia and chronic alcoholism [J]. Acta Cir Bras, 2018,33(8):652-663.
[7]Yang Q, Liang RX, Ye JX, et al. Experimental study on function of decreasing blood-lipid in hyperlipidemia rats and safety by extract of flos carthami [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2007, 13(11):30-33. (in Chinese)
杨庆, 梁日欣, 叶锦霞, 等. 红花提取物对高脂血症模型大鼠降血脂作用和安全性实验研究[J]. 中国实验方剂学杂志, 2007, 13(11):30-33.
[8]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.
[9]Choi BI, Park D, Lee SH, et al. Neurobehavioural deficits correlate with the cerebral infarction volume of stroke animals: a comparative study on ischaemia-reperfusion and photothrombosis models [J]. Environ Toxicol Pharmacol, 2012, 33(1):60-69.
[10]Jahan R, Saver JL, Schwamm LH, et al. Association between time to treatment with endovascular reperfusion therapy and outcomes in patients with acute ischemic stroke treated in clinical practice[J]. JAMA, 2019, 322(3):252-263.
[11]Enzmann G, Kargaran S, Engelhardt B. Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function[J].Ther Adv Neurol Disord,2018, 11:1-15.
[12]Lei M, Wu LR, Liu Y. Protective effect and molecular mechanism of losartan on cerebral ischemia reperfusioninjury in rats[J]. Chinese Journal of Arteriosclerosis, 2020, 28(3):213-218. (in Chinese)
雷敏, 吴丽荣, 刘英. 氯沙坦对大鼠脑缺血再灌注损伤的保护作用及分子机制[J]. 中国动脉硬化杂志, 2020, 28(3):213-218.
[13]Kotipatruni RR, Dasari VR, Veeravalli KK, et al. p53-and Bax-mediated apoptosis in injured rat spinal cord[J]. Neurochem Res, 2011, 36(11):2063-2074.
[14]Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death[J]. Nat Rev Mol Cell Biol, 2008, 9(1):47-59.
[15]Badr R, Hashemi M, Javadi G, et al. Assessment of global ischemic/reperfusion and tacrolimus administration on CA1 region of hippocampus: gene expression profiles of BAX and BCL2 genes [J]. Bratisl Lek Listy, 2016, 117(6):358-362.
[16]Xie YL, Zhang B, Jing L. MiR-125b blocks Bax/cytochrome C/Caspase-3 apoptotic signaling pathway in rat models of cerebral ischemia-reperfusion injury by targeting p53[J]. Neurol Res, 2018, 40(10): 828-837.
[17]Wang Y, He Y, Yang JH, et al. Effects of Yangyin Tongnao Granules on the expression of Caspase-3, Bax, Bcl-2 mRNA inrats after cerebral ischemia/reperfusion injury[J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2018, 33(9):3875-3878. (in Chinese)
王玉,何昱,杨洁红,等. 养阴通脑颗粒对大鼠脑缺血/再灌注损伤后Caspase-3、Bcl-2、Bax mRNA表达的影响[J]. 中华中医药杂志,2018, 33(9):3875-3878.
[18]Fifield KE, Rowe TM, Raman-Nair JB, et al. Prolonged high fat diet worsens the cellular response to a small, covert-like ischemic stroke[J]. Neuroscience, 2019, 406:637-652.
[19]Irving EA, Bamford M. Role of mitogen-and stress-activated kinases in ischemic injury [J]. J Cereb Blood Flow Metab, 2002, 22(6):631-647.
[20]Liu DR,  Hu W, Chen GZ. Apelin-12 exerts neuroprotective effect against ischemiareperfusion injury by inhibiting JNK and P38MAPK signaling pathway in mouse[J]. Eur Rev Med Pharmacol Sci, 2018, 22(12):3888-3895.
[21]Irving EA, Barone FC, Reith AD, et al. Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat[J]. Brain Res Mol Brain Res, 2000, 77(1): 65-75.
[22]Nito C, Kamada H, Endo H, et al. Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A2 signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion[J]. J Cereb Blood Flow Metab, 2008, 28(10): 1686-1696.
PDF(9812 KB)

Accesses

Citation

Detail

Sections
Recommended

/