Protective Effect and Mechanism of Nanoliposomal Quercetin on Focal Cerebral Ischemia-reperfusion Injury in Rats

doi:10.3969/j.issn.1674-5817.2020.02.005

Abstract

Abstract: Objective To study the neuroprotective effects and mechanism of nanoliposomal quercetin (nLQ) on focal cerebral ischemia-reperfusion injury in rats. Methods Eighty male SD rats were randomly divided into sham-operation group, model group, nLQ low-dose group, nLQ middle-dose group and nLQ high-dose group, with 16 rats in each group. The middle cerebral artery occlusion model was established by modified suture method. Fourty-eight hours after cerebral ischemia-reperfusion, the behavioral score was observed by using neurological deficit score method, the cerebral infarction volume was measured by TTC staining test, the water content of brain tissue was measured by wet and dry weight method, the contents of tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10) in serum were determined by ELASA assay, the neuronal apoptosis was detected by flow cytometry, and the expressions of Bcl-2 and Bax in brain tissue were detected by Western blotting. Results Compared with the model group rats, nLQ low, middle and high dose groups could significantly improve the neurological deficit symptoms, reduce the behavioral score, decrease the cerebral infarction volume and alleviate cerebral edema, reduce the contents of TNF-α and IL-10 in serum, reduce the rate of neuronal apoptosis, decrease Bax protein expression and increase Bcl-2 protein expression in brain tissue. The differences were statistically significant (P<0.05 or P<0.01), also with a dose-dependent manner. Conclusion The nLQ has a significant protective effect on the focal cerebral ischemia-reperfusion injury in rats. The nLQ may improve the neurological function, reduce the apoptosis of neuronal cells and decrease the content of inflammatory factors TNF- and IL-10 in blood.

Key words: Nanoliposomal quercetin, Cerebral ischemia-reperfusion injury, Apoptosis, Tumor necrosis factor α, Interleukin 10

CLC Number:

Q95-33

KANG Yu, YANG Xiaofang. Protective Effect and Mechanism of Nanoliposomal Quercetin on Focal Cerebral Ischemia-reperfusion Injury in Rats[J]. Laboratory Animal and Comparative Medicine, 2020, 40(2): 116-122.

References

[1] 马纳, 李亚静, 范吉平. 槲皮素药理作用研究进展[J]. 辽宁中医药大学学报, 2018, 20(8):221-224.
[2] Nikfarjam BA, Hajiali F, Adineh M, et al.Anti-inflammatory effects of quercetin and vitexin on activated human peripheral blood neutrophils[J]. J Pharmacopuncture, 2017, 20(2):127-131.
[3] Jin Z, Li F, Liao J, et al.Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo[J]. PLoS One, 2017, 12(3):e0172838.
[4] 陈振华, 胡晓艳, 赵滕, 等. 槲皮素对心血管系统疾病的影响及其新剂型研究进展[J]. 时珍国医国药, 2019, 30(2):440-443.
[5] 匡维新, 曹海平, 张晓旭, 等. 槲皮素对大鼠心肌缺血再灌注内质网应激的影响[J]. 世界最新医学信息文摘, 2018, 18(41):128-129.
[6] Zheng NG, Mo SJ, Li JP, et al.Anti-CSC effects in human esophageal squamous cell carcinomas and Eca109/9706 cells induced by nanoliposomal quercetin alone or combined with CD 133 antiserum[J]. Asian Pac J Cancer Prev, 2014, 15(20):8679-8684.
[7] Han Q, Wang XH, Cai SF, et al.Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity[J]. J Mater Chem B, 2018, 6(9):1-8.
[8] 姜素芳, 姚瑶, 丁燕飞, 等. 反相高效液相色谱法测定盐酸青藤碱纳米脂质体药物含量及包封率[J]. 中南药业, 2005, 3(4):213-215.
[9] Longa EZ, Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1):84-91.
[10] 彭俊亮, 祝美珍. 中医药治疗缺血性脑中风的研究概况[J]. 湖南中医杂志, 2019, 25(6):145-147.
[11] Zhao YN, Guo XF, Li JM, et al.mTOR/autophagy pathway in the hippocampus of rats suffering intermittent hypoxia preconditioning and global cerebral ischemia-reperfusion[J]. Oncotarget, 2017, 8(14):23353-23359.
[12] 冯亚莉, 吕小改, 翟广玉. 槲皮素酯的合成及清除自由基活性研究[J]. 化学与黏合, 2018, 40(6):415-419.
[13] 雷晓鸣, 孟丽华, 蒋文军, 等. 槲皮素对大鼠全脑缺血/再灌注损伤的保护作用[J]. 山西医科大学学报, 2019(9):1254-1261.
[14] 肖洁, 尹松梅, 谢双锋, 等. 槲皮素调控AMPK活性诱导HL-60细胞自噬与凋亡[J]. 中山大学学报: 医学版, 2018, 39(4):501-509.
[15] 孙卉, 滕浩, 杜密英, 等. 槲皮素降脂减肥机制研究进展[J]. 食品工业科技, 2019, 40(16):349-353, 362.
[16] 余浩佳, 冯向营, 辛世萌, 等. 丁苯酞注射液预处理通过NF-κB信号通路对大鼠脑缺血再灌注损伤的保护作用[J]. 中风与神经疾病杂志, 2015, 32(12):1119-1121.
[17] Maleki SN, Aboutaleb N, Souri F.Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines[J]. J Chem Neuroanat, 2018, 87:54-59.
[18] Hu QY, Ren HJ, Ren J, et al.Released mitochondrial DNA following intestinal ischemia reperfusion induces the inflammatory response and gut barrier dysfunction[J]. Sci Rep, 2018, 8(1):7350.
[19] 贾栋. 贝前列素钠对脑缺血再灌注损伤大鼠血清IL-6、TNF-α水平及MPO活性影响[J]. 中国医院药学杂志, 2015, 35(20):1874-1875.
[20] 吴建龙, 巨积辉, 周广良,等. SB202190对皮瓣缺血再灌注损伤时TNF-α和IL-10影响的实验研究[J]. 中国临床解剖学杂志, 2014, 32(6):698-703.
[21] Wan X, Huang WJ, Chen W, et al.IL-10 deficiency increases renal ischemia-reperfusion injury[J]. Nephron Exp Nephrol, 2014, 128(1/2): 37-45.
[22] 郭生龙, 陈瑞利, 雷琦, 等. 丁苯酞对小鼠脑缺血再灌注损伤细胞坏死性凋亡的影响[J]. 中华行为医学与脑科学杂志, 2019, 28(2):122-126.
[23] Zhao T, Fu Y, Sun H, et al.Ligustrazine suppresses neuron apoptosis via the Bax/Bcl-2 and caspase-3 pathway in PC12 cells and in rats with vascular dementia[J]. IUBMB Life, 2018, 70(1):60-70.
[24] Liu R, Zhong X, Zeng J, et al.3'-Daidzein sulfonate sodium inhibits neuronal apoptosis induced by cerebral ischemia-reperfusion[J]. Int J Mol Med, 2017, 39(4):1021-1028.