党参多糖介导Nrf2通路对缺氧缺血性脑损伤的抗氧化和神经保护作用
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摘要
目的研究党参多糖对缺氧缺血性脑损伤的抗氧化和神经保护作用及其机制。方法采用Rice法建立HIBI模型。假手术组和模型组灌胃给予生理盐水,模型加药组灌胃给予党参多糖。分别进行神经功能学评分,观察脑积水量,脑组织病理学改变,神经元细胞凋亡情况,脑组织脂质过氧化物水平,抗氧化和神经保护相关蛋白表达水平。结果党参多糖能显著改善模型大鼠神经功能、脑水肿(P<0.01)和病理改变,降低细胞凋亡率(P<0.01)和Bax表达(P<0.01),降低LDH和MDA含量(P<0.01);同时,上调Bcl-2表达(P<0.01)和SOD活性(P<0.01),增加bFGF、BDNF、PSD95、SYP、Nrf2和HO-1表达(P<0.01)。结论党参多糖对缺氧缺血性脑损伤具有抗氧化和神经保护作用,可能与介导Nrf2信号通路相关。
Objective To study the antioxidant and neuroprotective effects of Codonopsis pilosula polysaccharides(CPP) and its possible mechanism. Methods Rice method was used to establish HIBI rat model. Normal saline was given to the sham group and the HIBI group, and corresponding doses of CPP solution were given to the drug groups. The neurological function, cerebral water content of rats,histopathologic changes, apoptosis in the rat hippocampus, the level of lipid peroxide, the expression of antioxidant and neuroprotective proteins were evaluated. Results Compared with the model group, the neurological function, cerebral water content and the pathological injury of brain tissue were significantly reduced(P<0.01). The apoptosis rate, expression of Bax, content of LDH and MDA also decreased significantly(P<0.01). Expression of Bcl-2 and activity of SOD were up-regulated(P<0.01). In addition, the expressions of bFGF, BDNF, PSD95, SYP, Nrf2 and HO-1 were significantly up-regulated(P<0.01).Conclusion CPP has antioxidant and neuroprotective effects on hypoxic-ischemic brain injury, and its function may be related to mediating Nrf2 signal pathway.
Objective To study the antioxidant and neuroprotective effects of Codonopsis pilosula polysaccharides(CPP) and its possible mechanism. Methods Rice method was used to establish HIBI rat model. Normal saline was given to the sham group and the HIBI group, and corresponding doses of CPP solution were given to the drug groups. The neurological function, cerebral water content of rats,histopathologic changes, apoptosis in the rat hippocampus, the level of lipid peroxide, the expression of antioxidant and neuroprotective proteins were evaluated. Results Compared with the model group, the neurological function, cerebral water content and the pathological injury of brain tissue were significantly reduced(P<0.01). The apoptosis rate, expression of Bax, content of LDH and MDA also decreased significantly(P<0.01). Expression of Bcl-2 and activity of SOD were up-regulated(P<0.01). In addition, the expressions of bFGF, BDNF, PSD95, SYP, Nrf2 and HO-1 were significantly up-regulated(P<0.01).Conclusion CPP has antioxidant and neuroprotective effects on hypoxic-ischemic brain injury, and its function may be related to mediating Nrf2 signal pathway.
引文
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[3]Zhang Y,Tie X,Bao B,et al.Metabolism of flavones C-glucosides and p-coumaric acid from antioxidant of bamboo leaves(AOB)in rats[J].Br J Nutr,2007,97(3):484-494.
[4]Yue T,Shao D,Yuan Y,et al.Ultrasound-assisted extraction,HPLCanalysis,and antioxidant activity of polyphenols from unripe apple[J].JSep Sci,2012,35(16):2138-2145.
[5]Xie JH,Shen MY,Xie MY,et al.Ultrasonic-assisted extraction,antimicrobial and antioxidant activities of Cyclocarya paliurus(Batal.)Iljinskaja polysaccharides[J].Carbohydr Polym,2012,89(1):177-184.
[6]Liu JH,Li L,Shang XD,et al.Anti-Helicobacter pylori activity of bioactive components isolated from Hericiumerinaceus[J].J Ethnopharmacol,2016,183(1):54-58.
[7]Rajagopalu D,Show PL,Tan YS,et al.Recovery of laccase from processed Hericium erinaceus(Bull.:Fr)Pers.Fruitingbodies in aqueous two-phase system[J].J Biosci Bioeng,2016,122(3):301-306.
[8]Zhang P,Hu L,Bai R,et al.Structural characterization of a pectic polysaccharide from Codonopsis pilosulaand its immunomodulatory activities in vivo and in vitro[J].Int J Biol Macromol,2017,104(Pt A):1359-1369.
[9]Liu C,Chen J,Li E,et al.Solomonseal polysaccharide and sulfated Codonopsis pilosula polysaccharidesynergistically resist Newcastle disease virus[J].PLoS One,2015,10(2):e0117916.
[10]Liu C,Chen J,Li E,et al.The comparison of antioxidative and hepatoprotective activities of Codonopsispilosula polysaccharide(CP)and sulfated CP[J].Int Immunopharmacol,2015,24(2):299-305.
[11]Chu X,Liu XJ,Qiu JM,et al.Inhibitory effects of codonopsis pilosula polysaccharides on the deterioration of impaired phagocytosis of alveolar macrophage induced by fine particulate matter in chronic obstructive pulmonary disease mice[J].Zhonghua Yi Xue Za Zhi,2016,96(14):1134-1138.
[12]Chu X,Liu XJ,Qiu JM,et al.Effects of Astragalus and Codonopsis pilosula polysaccharides on alveolar macrophage phagocytosis and inflammation in chronic obstructive pulmonary disease mice exposed to PM2.5[J].Environ Toxicol Pharmacol,2016,48(1):76-84.
[13]Zhang Q,Xia Y,Luo H,et al.Codonopsis pilosula polysaccharide attenuates tau hyperphosphorylation and cognitive impairments in htau infected mice[J].Front Mol Neurosci,2018,11(1):437.
[14]Ma Q,Dasgupta C,Li Y,et al.Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats[J].Neurobiol Dis,2016,89(1):202-212.
[15]Ma Q,Dasgupta C,Li Y,et al.MicroRNA-210 suppresses junction proteins and disrupts blood-brain barrier integrity in neonatal rat hypoxic-ischemic brain injury[J].Int J Mol Sci,2017,18(7):E1356.
[16]Bederson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of aneurologic examination[J].Stroke,1986,17(3):472-476.
[17]Li ZW,Zheng XN,Li P,et al.Time-effect relationship of acupuncture on histopathology,ultrastructure,and neuroethology in the acute phase of cerebral hemorrhage[J].Neural Regen Res,2019,14(1):107-113.
[18]Zhang Y,Yang X,Jin G,et al.Polysaccharides from Pleurotus ostreatus alleviate cognitive impairment in a ratmodel of Alzheimer's disease[J].Int J Biol Macromol,2016,92(1):935-941.
[19]Ho YS,Yu MS,Yang XF,et al.Neuroprotective effects of polysaccharides from wolfberry,the fruits of Lyciumbarbarum,against homocysteine-induced toxicity in rat cortical neurons[J].J Alzheimers Dis,2010,19(3):813-827.
[20]Qin T,Ren Z,Liu X,et al.Study of the selenizing Codonopsis pilosula polysaccharides protects RAW264.7 cells from hydrogen peroxideinduced injury[J].Int J Biol Macromol,2019,125(3):534-543.
[21]Siuda J,Patalong-Ogiewa M,muda W,et al.Cognitive impairment and BDNF serum levels[J].Neurol Neurochir Pol,2017,51(1):24-32.
[22]Whitfield DR,Vallortigara J,Alghamdi A,et al.Assessment of ZnT3and PSD95 protein levels in Lewy body dementias and Alzheimer's disease:association with cognitive impairment[J].Neurobiol Aging,2014,35(12):2836-2844.
[23]Han XF,Zhang Y,Xiong LL,et al.Lentiviral-mediated netrin-1overexpression improves motor and sensory functions in SCT rats associated with SYP and GAP-43 expressions[J].Mol Neurobiol,2017,54(3):1684-1697.
[24]Yu R,Chen C,Mo YY,et al.Activation of mitogen-activated protein kinase pathways induces antioxidantresponse element-mediated gene expression via a Nrf2-dependent mechanism[J].J Biol Chem,2000,275(51):39907-39913.
[25]Paine A,Eiz-Vesper B,Blasczyk R,et al.Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential[J].Biochem Pharmacol,2010,80(12):1895-1903.
[26]Tong KI,Kobayashi A,Katsuoka F,et al.Two-site substrate recognition model for the Keap1-Nrf2 system:a hinge and latch mechanism[J].Biol Chem,2006,387(10-11):1311-1320.
[27]Kensler TW,Wakabayashi N,Biswal S.Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway[J].Annu Rev Pharmacol Toxicol,2007,47(1):89-116.