Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect

GAO Sai-Hong; ZHANG Xiao-Liang; YANG Ying-Chun; QIAO Hai-Bing

doi:10.16098/j.issn.0529-1356.2023.02.007

PDF(6795 KB)

Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (2) : 175-180. DOI: 10.16098/j.issn.0529-1356.2023.02.007

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect

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

Author information +

History +

Abstract

Objective To observe the effect of polyinosinic-polycytidylic acid (Poly-IC) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion （I/R）injury in hyperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I/R injury in hyperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I/R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly(P<0.05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group(P<0.05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0.05), and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability(P<0.05). No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0.05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group (P<0.05), while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0.05). The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0.05), the expression of Bcl-2 was significantly decreased(P<0.05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly(P<0.05), the expression of Bcl-2 increased significantly(P<0.05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.

Key words

Hyperlipidemia

/ Cerebral ischemia-reperfusion / Polyinosinic-polycytidylic acid / B-cell lymphoma-2 / Bcl-2 assaciated X protein / Terminal UTP nickend labeling / Rat

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

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

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect

[J]. Acta Anatomica Sinica. 2023, 54(2): 175-180 https://doi.org/10.16098/j.issn.0529-1356.2023.02.007

References

［1］Feigin VL, Krishnamurthi RV, Parmar P, et al. Update on the global burden of ischemic and hemorrhagic stroke in 19902013: The GBD 2013 Study［J］. Neuroepidemiology, 2015, 45(3):161-176.

［2］Chen YY, Zhang YH, Xu L, et al. Effect of tongluoqingnao powder injection on protecting the brain and expression of neuronic autophagy-related proteins in a rat model of cerebral ischemia-reperfusion injury［J］. Chinese General Practice, 2021, 24(15):1951-1958. (in Chinese)

陈琰琰, 张业昊, 徐立, 等. 通络清脑注射粉针对脑缺血-再灌注损伤大鼠的脑保护作用及神经元自噬相关蛋白表达的影响研究［J］. 中国全科医学, 2021, 24(15):1951-1958.

［3］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.

［4］Gao SH, Ren ZhCh, Zhang XL, et al. Hyperlipemia affects the expression of MMP-9 in the cerebral cortex after cerebral ischemia-reperfusion injury in rats ［J］. Chinese Journal of Anatomy, 2015, 38(6):685-688,693. (in Chinese)

高赛红, 任占川, 张小良, 等. 高血脂对大鼠脑缺血再灌注损伤后大脑皮质基质金属蛋白酶9表达的影响［J］. 解剖学杂志, 2015, 38(6):685-688,693.

［5］Chen EY, Chen C, Niu ZD, et al. Poly (I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway［J］. Signal Transduct Target Ther, 2020, 5(1):216.

［6］Li Y, Xu XL, Zhao D, et al. TLR3 ligand poly IC attenuates reactive astrogliosis and improves recovery of rats after focal cerebral ischemia［J］. CNS Neurosci Ther, 2015, 21(11):905-913.

［7］Ramnath D, Powell EE, Scholz GM, et al. The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair［J］. Semin Cell Dev Biol, 2017, 61:22-30.

［8］Wang PF, Fang H, Chen J, et al. Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3 ［J］. J Immunol, 2014, 192(10):4783-4794.

［9］Liu ZX, Zhang ZW, Zhou XH, et al. Neuroprotective effect of γ-secretase inhibitors on neural stem cells after cerebral ischemia in rats［J］. Acta Anatomica Sinica, 2019, 50(2):145-151. (in Chinese)

刘宗秀, 张紫微, 周晓红, 等. γ-分泌酶抑制剂对脑缺血大鼠神经干细胞移植后神经保护作用［J］. 解剖学报, 2019, 50(2):145-151.

［10］Gu Y, Chen X, Fu SP, et al. Astragali radix isoflavones synergistically alleviate cerebral ischemia and reperfusion injury via activating estrogen receptor-PI3K-Akt signaling pathway［J］. Front Pharmacol, 2021, 12:533028.

［11］Dhanesha N, Ahmad A, Prakash P, et al. Genetic ablation of extra domain a of fibronectin in hypercholesterolemic mice improves stroke outcome by reducing thrombo-inflammation［J］. Circulation, 2015, 132(23): 2237-2247.

［12］Pikija S, Sztriha LK, Killer-Oberpfalzer M, et al. Contribution of serum lipid profiles to outcome after endovascular thrombectomy for anterior circulation ischemic stroke ［J］. Mol Neurobiol, 2019, 56(6):4582-4588.

［13］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.

［14］Toell T, Mayer L, Pechlaner R, et al. Familial hypercholesterolaemia in patients with ischemic stroke or transient ischemic attack［J］. Eur J Neurol, 2018, 25(2):260-267.

［15］Xue NY, Ren XJ. Effect of electroacupuncture on GFAP in hippocampal dentate gyrus(DG) of rats with hyperlipidemia and middle cerebral ischemia［J］. Journal of Beijing University of Traditional Chinese Medicine, 2020, 43(4):327-333. (in Chinese)

薛娜英, 任秀君. 电针对高血脂合并脑缺血大鼠海马齿状回星形胶质细胞活化的影响［J］. 北京中医药大学学报, 2020, 43(4):327-333.

［16］Wu JJ, Zong HB, Lu T, et al. Poly-IC protects the spinal cord in inflammatory response to ischemia-reperfusion injury in rats［J］. J Med Postgra, 2017, 30(6):596-600. (in Chinese)

武建杰, 宗海斌, 路坦, 等. 多聚肌苷酸多聚胞苷酸对大鼠脊髓缺血/再灌注损伤后炎性反应的脊髓保护作用［J］. 医学研究生学报, 2017, 30(6):596-600.

［17］Li L, Acioglu C, Heary RF, et al. Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases［J］. Brain Behav Immun, 2021, 91:740-755.

［18］Pan LN, Zhu W, Li C, et al. Toll-like receptor 3 agonist Poly I:C protects against simulated cerebral ischemia in vitro and in vivo［J］. Acta Pharmacol Sin, 2012, 33(10):1246-1253.

［19］Zhang X, Ha TZh, Lu C, et al. Poly (I:C) therapy decreases cerebral ischaemia/reperfusion injury via TLR3-mediated prevention of Fas/FADD interaction［J］. J Cell Mol Med, 2015, 19(3):555-565.

［20］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.

［21］Kuo PCh, Weng WT, Scofield BA, et al. Interferon-β alleviates delayed tPA-induced adverse effects via modulation of MMP3/9 production in ischemic stroke［J］. Blood Adv, 2020, 4(18):4366-4381.

［22］Packard AE, Hedges JC, Bahjat FR, et al. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury［J］. J Cereb Blood Flow Metab, 2012, 32(2):242-247.

［23］Pan LN, Zhu W, Li Y, et al. Astrocytic Toll-like receptor 3 is associated with ischemic preconditioning-induced protection against brain ischemia in rodents［J］. PLoS One, 2014, 9(6):e99526.