壳寡糖对镉致肝脏损伤的保护作用及机理研究
Chitooligosaccharide Alleviation on Cadmium-induced Liver Injury
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摘要: 为研究壳寡糖(chitooligosaccharide,COS)对镉致肝脏损伤的作用及机制,选用32只体质量在16~19 g的健康雌性C57BL/6小鼠,随机分为4个组:空白对照组(Control)、氯化镉造模组(Cd)、壳寡糖组(COS)、壳寡糖+氯化镉组(COS+Cd)。空白对照组和氯化镉造模组每日饲喂基础日粮,饮用纯净水;壳寡糖组和壳寡糖+氯化镉组每日饲喂基础日粮,在饮水中添加0.3 g·L-1 COS。于第28天对氯化镉造模组和壳寡糖+氯化镉组小鼠采取腹腔注射5.45 mg·kg-1氯化镉的处理,12 h后采样。结果显示:(1)添加COS缓解了重金属镉累积导致的肝细胞颗粒变性、细胞结构模糊等病理症状;(2) COS缓解了由于重金属镉暴露导致的氧化应激,激活了小鼠体内的氧化型谷胱甘肽(oxidized glutathione,GSSG)/谷胱甘肽(glutathione,GSH)系统(P<0.05),显著减少了肝脏由于氧化损伤而产生的活性氧(reactive oxygen species,ROS)(P<0.05),有利于缓解肝脏由于重金属富集而导致的肝脏氧化损伤;(3)镉暴露使小鼠肝脏细胞中Nrf2的水平显著升高(P<0.01),提高了机体应激信号通路关键分子p38 MAPK的磷酸化水平(P<0.05),同时抑制了关键炎症信号分子p-NF-кB p65(P<0.05)。综上可知,COS可通过调控p38 MAPK/NF-кB p65/Nrf2等关键因子的表达缓解镉对肝脏的氧化损伤,从而达到对肝脏的保护作用。Abstract: This research aims to study the effect and mechanism of chitooligosaccharide (COS) on alleviating liver injury induced by cadmium. A total of 32 healthy female C57BL/6 mice with a body weight of 16 to 19 g were randomly divided into four groups:Control group (Control), cadmium chloride model group (Cd), COS group (COS), and COS+cadmium chloride group (COS+Cd). Control group and cadmium chloride model group were fed basal diet and pure water every day. Mice in the COS group and the COS+Cd group were fed a basal diet and pure water with 0.3 g·L-1 COS. On the 28th day of the experiment, mice in the Cd group and the COS+Cd group were intraperitoneally injected with 5.45 mg·kg-1 CdCl2 and sampled 12 h later. The results showed that:(1) COS supplement alleviated the pathological symptoms of liver cell granule degeneration, and repaired the cellular structure caused by cadmium induction. (2) COS supplement alleviated the oxidative stress caused by cadmium induction, activated the oxidized glutathione (GSSG)/glutathione (GSH) system in mice (P<0.05), and significantly reduced the reactive oxygen species (ROS) in the liver (P<0.05). It is beneficial to alleviate liver damage caused by heavy metal exposure. (3) Cd induction significantly increased the relative level of Nrf2 in the liver (P<0.01), activated the relative expression of phosphorylated p38 MAPK, a key molecule of stress signaling pathway (P<0.05), and inhibited the phosphorylated NF-кB p65 (P<0.05). In conclusion, COS supplement could alleviate oxidative damage in the liver induced by cadmium via regulating the expression of key factors, such as p38 MAPK/NF-кB p65/Nrf2, then achieving a protective effect.
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Key words:
- cadmium /
- liver cells of mouse /
- acute toxicity /
- chitooligosaccharide /
- oxidative stress
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Yang R Y, He Y H, Luo L F, et al. The interaction between selenium and cadmium in the soil-rice-human continuum in an area with high geological background of selenium and cadmium[J]. Ecotoxicology and Environmental Safety, 2021, 222:112516 DalCorso G, Fasani E, Manara A, et al. Heavy metal pollutions:State of the art and innovation in phytoremediation[J]. International Journal of Molecular Sciences, 2019, 20(14):3412 Vesna M, Aleksandra B, Danijela D, et al. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys[J]. Food and Chemical Toxicology:An International Journal Published for the British Industrial Biological Research Association, 2015, 78:130-140 Wang K, Ma J Y, Li M Y, et al. Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells:Oxidative stress, cell cycle arrest and apoptosis[J]. Science of the Total Environment, 2021, 756:143951 Chang C, Yin R S, Zhang H, et al. Bioaccumulation and health risk assessment of heavy metals in the soil-rice system in a typical seleniferous area in central China[J]. Environmental Toxicology and Chemistry, 2019, 38(7):1577-1584 Gupta N, Yadav K K, Kumar V, et al. Trace elements in soil-vegetables interface:Translocation, bioaccumulation, toxicity and amelioration:A review[J]. Science of the Total Environment, 2019, 651:2927-2942 Pecina V, Brtnický M, Baltazár T, et al. Human health and ecological risk assessment of trace elements in urban soils of 101 cities in China:A meta-analysis[J]. Chemosphere, 2021, 267:129215 Knoell D L, Wyatt T A. The adverse impact of cadmium on immune function and lung host defense[J]. Seminars in Cell & Developmental Biology, 2021, 115:70-76 王莉, 闻双全, 贺双江, 等. 慢性镉暴露对小鼠大脑皮质的毒性损伤作用[J]. 畜牧与兽医, 2021, 53(2):50-55 Wang L, Wen S Q, He S J, et al. Toxic damage effect of chronic cadmium exposure on the cerebral cortex of mouse[J]. Animal Husbandry & Veterinary Medicine, 2021, 53(2):50-55(in Chinese)
龚频, 高浩天, 杨文娟, 等. 蓝莓花青素对镉致小鼠心脏损伤的改善作用[J]. 陕西科技大学学报, 2020, 38(6):48-53 Gong P, Gao H T, Yang W J, et al. The amelioration effect of blueberry anthocyanins on cadmium-induced mice heart damage[J]. Journal of Shaanxi University of Science & Technology, 2020, 38(6):48-53(in Chinese)
陶灿. 日粮镉对蛋鸡生产性能、蛋品质、肝脏和肾脏的影响[D]. 武汉:华中农业大学, 2019:42 Tao C. Effects of dietary cadmium on performance, egg quality, liver and kidney damage of laying hens[D]. Wuhan:Huazhong Agricultural University, 2019:42(in Chinese) Marín-García J, Akhmedov A T. Mitochondrial dynamics and cell death in heart failure[J]. Heart Failure Reviews, 2016, 21(2):123-136 张文华, 闻双全, 王莉, 等. 葛根素对镉致大鼠肝毒性损伤的保护作用[J]. 中国兽医科学, 2020, 50(10):1333-1339 Zhang W H, Wen S Q, Wang L, et al. Protective effect of puerarin on toxic damage caused by cadmium in livers of rats[J]. Chinese Veterinary Science, 2020, 50(10):1333-1339(in Chinese)
Wan J, Xu Q S, He J. Maternal chitosan oligosaccharide supplementation during late gestation and lactation affects offspring growth[J]. Italian Journal of Animal Science, 2018, 17(4):994-1000 Gu M, Pan S H, Li Q, et al. Chitosan and chitooligosaccharides attenuate soyabean meal-induced intestinal inflammation of turbot (Scophthalmus maximus):Possible involvement of NF-кB, activator protein-1 and mitogen-activated protein kinases pathways[J]. British Journal of Nutrition, 2021, 126(11):1651-1662 Ahmed S M U, Luo L, Namani A, et al. Nrf2 signaling pathway:Pivotal roles in inflammation[J]. Biochimica et Biophysica Acta Molecular Basis of Disease, 2017, 1863(2):585-597 Wang Y M, Xiong Y L, Zhang A P, et al. Oligosaccharide attenuates aging-related liver dysfunction by activating Nrf2 antioxidant signaling[J]. Food Science & Nutrition, 2020, 8(7):3872-3881 彭媛媛, 欧阳富龙, 贺建华. 壳寡糖在动物体内抗氧化功能研究进展[J]. 饲料博览, 2015(8):16-18 Peng Y Y, Ouyang F L, He J H. Research advances of chitosan oligosaccharide on the antioxidant function in animal[J]. Feed Review, 2015 (8):16-18(in Chinese)
郑雯静, 杨靖亚, 刘克海. 壳寡糖对三氧化二砷致大鼠肝细胞毒性的保护作用[J]. 安徽农业大学学报, 2021, 48(3):412-417 Zheng W J, Yang J Y, Liu K H. Protective effect of chitosan oligosaccharide against the toxicity of arsenic trioxide toward Buffalo rat liver cells[J]. Journal of Anhui Agricultural University, 2021, 48(3):412-417(in Chinese)
Zhao Q N, Yin L Q, Zhang L R, et al. Chitoheptaose promotes heart rehabilitation in a rat myocarditis model by improving antioxidant, anti-inflammatory, and antiapoptotic properties[J]. Oxidative Medicine and Cellular Longevity, 2020, 2020:2394704 孙继鹏. 壳寡糖金属配合物对扇贝体内重金属镉的影响[D]. 青岛:中国海洋大学, 2009:14 Sun J P. The effect of chitosan oligosaccharide complexes with metal elements on cadmium in viscera of Chlamys ferrari[D]. Qingdao:Ocean University of China, 2009:14(in Chinese) Montes S, Juárez-Rebollar D, Nava-Ruíz C, et al. Immunohistochemical study of Nrf2-antioxidant response element as indicator of oxidative stress induced by cadmium in developing rats[J]. Oxidative Medicine and Cellular Longevity, 2015, 2015:570650 Zhang Y T, Ahmad K A, Khan F U, et al. Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway[J]. Chemico-Biological Interactions, 2019, 305:54-65 Rius-Pérez S, Pérez S, Martí-Andrés P, et al. Nuclear factor kappa B signaling complexes in acute inflammation[J]. Antioxidants & Redox Signaling, 2020, 33(3):145-165 Kim E K, Choi E J. Pathological roles of MAPK signaling pathways in human diseases[J]. Biochimica et Biophysica Acta, 2010, 1802(4):396-405 Gorska M M, Liang Q L, Stafford S J, et al. MK2 controls the level of negative feedback in the NF-κB pathway and is essential for vascular permeability and airway inflammation[J]. Journal of Experimental Medicine, 2007, 204(7):1637-1652 Cheng C Y, Mruk D D. The blood-testis barrier and its implications for male contraception[J]. Pharmacological Reviews, 2012, 64(1):16-64 Huang G Q, Sun J P, Wang D F, et al. Chitosan oligosaccharide-Ca complex accelerates the depuration of cadmium from Chlamys ferrari[J]. Journal of Ocean University of China, 2012, 11(2):219-226 Nguyen T, Nioi P, Pickett C B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress[J]. Journal of Biological Chemistry, 2009, 284(20):13291-13295 Radan M, Dianat M, Badavi M, et al. In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10):The effective role of gallic acid[J]. Free Radical Research, 2019, 53(2):210-225 Ren L F, Qi K, Zhang L, et al. Glutathione might attenuate cadmium-induced liver oxidative stress and hepatic stellate cell activation[J]. Biological Trace Element Research, 2019, 191(2):443-452 Kaspar J W, Niture S K, Jaiswal A K. Nrf2:INrf2(Keap1) signaling in oxidative stress[J]. Free Radical Biology and Medicine, 2009, 47(9):1304-1309 Ben P L, Zhang Z P, Zhu Y Y, et al. L-theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation[J]. NeuroToxicology, 2016, 57:95-103 Mohajeri M, Rezaee M, Sahebkar A. Cadmium-induced toxicity is rescued by curcumin:A review[J]. BioFactors, 2017, 43(5):645-661 Chen X M, Bi M Y, Yang J, et al. Cadmium exposure triggers oxidative stress, necroptosis, Th1/Th2 imbalance and promotes inflammation through the TNF-α/NF-κB pathway in swine small intestine[J]. Journal of Hazardous Materials, 2022, 421:126704 Adamse P, van der Fels-Klerx H J I, Jong J D. Cadmium, lead, mercury and arsenic in animal feed and feed materials-trend analysis of monitoring results[J]. Food Additives & Contaminants Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment, 2017, 34(8):1298-1311 Ma X Q, Hou M, Liu C B, et al. Cadmium accelerates bacterial oleic acid production to promote fat accumulation in Caenorhabditis elegans[J]. Journal of Hazardous Materials, 2022, 421:126723 Kuester R K, Waalkes M P, Goering P L, et al. Differential hepatotoxicity induced by cadmium in Fischer 344 and Sprague-Dawley rats[J]. Toxicological Sciences, 2002, 65(1):151-159 Yeh C M, Hsiao L J, Huang H J. Cadmium activates a mitogen-activated protein kinase gene and MBP kinases in rice[J]. Plant and Cell Physiology, 2004, 45(9):1306-1312 陈梦妍, 谢佳, 田丽, 等. ZKSCAN3介导的自噬在急性镉暴露肝毒性中的作用[J]. 局解手术学杂志, 2020, 29(12):944-949 Chen M Y, Xie J, Tian L, et al. Effect of ZKSCAN3 mediated autophagy in acute cadmium exposure-induced liver injury[J]. Journal of Regional Anatomy and Operative Surgery, 2020, 29(12):944-949(in Chinese)
Sun X R, Su F M, Chen X L, et al. Doppler ultrasound and photoplethysmographic assessment for identifying pregnancy-induced hypertension[J]. Experimental and Therapeutic Medicine, 2020, 19(3):1955-1960 Affinati A H, Auchus R J. Endocrine causes of hypertension in pregnancy[J]. Gland Surgery, 2020, 9(1):69-79 Silva N S D, Araújo N K, Daniele-Silva A, et al. Antimicrobial activity of chitosan oligosaccharides with special attention to antiparasitic potential[J]. Marine Drugs, 2021, 19(2):110 Xie W M, Xu P X, Liu Q. Antioxidant activity of water-soluble chitosan derivatives[J]. Bioorganic & Medicinal Chemistry Letters, 2001, 11(13):1699-1701 Zhang X Y, Yang H B, Zheng J P, et al. Chitosan oligosaccharides attenuate loperamide-induced constipation through regulation of gut microbiota in mice[J]. Carbohydrate Polymers, 2021, 253:117218 许青松, 宫德正, 邹原, 等. 两种壳寡糖对急性肝损伤模型小鼠的保护作用[J]. 医药导报, 2008, 27(2):153-155 Xu Q S, Gong D Z, Zou Y, et al. Protective effect of two types of oligochitosans on CCl4-induced acute liver injury in mice[J]. Herald of Medicine, 2008, 27(2):153-155(in Chinese)
Azuma K, Osaki T, Minami S, et al. Anticancer and anti-inflammatory properties of chitin and chitosan oligosaccharides[J]. Journal of Functional Biomaterials, 2015, 6(1):33-49 朱常龙, 汪东风, 孙继鹏, 等. 壳寡糖配合物对扇贝产品中镉的脱除作用[J]. 农产品加工:创新版, 2010(7):10-13, 20 Zhu C L, Wang D F, Sun J P, et al. The removal of cadmium from Chlamys ferrari by chitosan oligosaccharide complexes with Ca and Mg[J]. Innovational Edition of Farm Products Processing, 2010(7):10-13, 20(in Chinese)
Liu J, Qu W, Kadiiska M B. Role of oxidative stress in cadmium toxicity and carcinogenesis[J]. Toxicology and Applied Pharmacology, 2009, 238(3):209-214 Fernandes J C, Eaton P, Nascimento H, et al. Antioxidant activity of chitooligosaccharides upon two biological systems:Erythrocytes and bacteriophages[J]. Carbohydrate Polymers, 2010, 79(4):1101-1106 Qiao Y, Bai X F, Du Y G. Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress[J]. International Immunopharmacology, 2011, 11(1):121-127 翟星辰. 壳寡糖免疫增强及对肾癌抑制作用的研究[D]. 哈尔滨:哈尔滨工业大学, 2019:71-72 Zhai X C. Research on immune enhancement of chitosan oligosaccharides and its inhibitory effects against renal carcinoma[D]. Harbin:Harbin Institute of Technology, 2019:71 -72(in Chinese)
张梦龙, 赵璧忱, 邢菲菲, 等. 热休克蛋白27通过调节氧化应激影响奶牛胎衣不下发生机制研究[J]. 黑龙江八一农垦大学学报, 2021, 33(1):21-26 , 75 Zhang M L, Zhao B C, Xing F F, et al. Mechanism of retained fetal membranes in cow affected by HSP27 through regulating oxidative stress[J]. Journal of Heilongjiang Bayi Agricultural University, 2021, 33(1):21-26, 75(in Chinese)
Beiraghi-Toosi A, Askarian R, Sadrabadi Haghighi F, et al. Burn-induced oxidative stress and serum glutathione depletion; a cross sectional study[J]. Emergency, 2018, 6(1):e54 Copple I M, Goldring C E, Kitteringham N R, et al. The Keap1-Nrf2 Cellular Defense Pathway:Mechanisms of Regulation and Role in Protection against Drug-Induced Toxicity[M]//Uetrecht J. Handbook of Experimental Pharmacology. Springer, 2010:233-266 Wu K C, Liu J J, Klaassen C D. Nrf2 activation prevents cadmium-induced acute liver injury[J]. Toxicology and Applied Pharmacology, 2012, 263(1):14-20 Casalino E, Calzaretti G, Landriscina M, et al. The Nrf2 transcription factor contributes to the induction of alpha-class GST isoenzymes in liver of acute cadmium or manganese intoxicated rats:Comparison with the toxic effect on NAD(P)H:Quinone reductase[J]. Toxicology, 2007, 237(1-3):24-34 李凯群. 高胆固酵通过激活ROS介导的NF-кB通路抑制肌腱干细胞的腱系分化[D]. 广州:南方医科大学, 2019:40-41 Li K Q. High cholesterol inhibits tenogenic differentiation in tendon-derived stem cells through ROS-activated NF-κB signaling[D]. Guangzhou:Southern Medical University, 2019 :40-41(in Chinese)
Luo Z G, Dong X X, Ke Q, et al. Chitooligosaccharides inhibit ethanol-induced oxidative stress via activation of Nrf2 and reduction of MAPK phosphorylation[J]. Oncology Reports, 2014, 32(5):2215-2222 Shaw P, Chattopadhyay A. Nrf2-ARE signaling in cellular protection:Mechanism of action and the regulatory mechanisms[J]. Journal of Cellular Physiology, 2020, 235(4):3119-3130 林谦, 邱磊, 云龙, 等. 核因子E2相关因子2调控机体抗氧化途径特性及其与畜禽的健康和肉品质的关系[J]. 动物营养学报, 2014, 26(6):1421-1429 Lin Q, Qiu L, Yun L, et al. Nuclear factor erythroid-2-related factor 2 mediated antioxidant pathway character and its relation on health and meat quality of livestock and poultry[J]. Chinese Journal of Animal Nutrition, 2014, 26(6):1421-1429(in Chinese)
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