柴胡多糖通过抑制氧化应激和炎症反应减轻铅诱导小鼠肝肾损伤的研究

doi:10.11843/j.issn.0366-6964.2021.09.030

摘要/Abstract

摘要： 本研究旨在探讨柴胡多糖对铅诱导小鼠肝肾损伤的影响。选取150只SPF级雄性健康昆明小鼠，适应性饲养2周后，随机分成5组，分别为对照组，铅处理组，铅处理+柴胡多糖低、中、高剂量组（100、200和400 mg·kg^-1）。铅染毒模型建立：小鼠每天饮铅水（醋酸铅0.5%），连续4周，建模结束后，试验组（铅处理+柴胡多糖组）每隔1 d灌胃柴胡多糖1次，连续2周，对小鼠血液及组织中铅含量及体质量进行测定，对抗氧化酶活性、脂质过氧化水平及炎症因子进行检测和分析，并从分子水平分析氧化损伤和炎症反应相关因子mRNA相对表达量。结果表明，与铅处理组相比，柴胡多糖可抑制铅中毒小鼠体重的下降和肝、肾脏器系数的升高，添加柴胡多糖使小鼠血液及组织中铅浓度略降低，但效果不显著（P>0.05）；与铅处理组相比，柴胡多糖可使染铅小鼠肝、肾组织的超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）及过氧化物酶（CAT）活性显著提高（P<0.05），丙二醛（MDA）含量降低；柴胡多糖可显著降低铅诱导小鼠血清和肝组织中丙氨酸转移酶（ALT）和谷草转移酶（AST）活力的升高，使小鼠血清血尿素氮（BUN）、肌酐（Scr）水平降低，肝、肾组织肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）、髓过氧化物酶（MPO）活性显著下降（P<0.05）；柴胡多糖能显著提高Nrf2信号通路的表达，使其HO-1、Cu/Zn-SOD、Mn-SOD、CAT mRNA水平上升，降低Keap1 mRNA水平，此外，柴胡多糖能明显降低铅诱导小鼠肝、肾炎症因子NF-κB、IL-1β及TNF-α mRNA水平上升（P<0.05）。综上表明，低、中、高剂量柴胡多糖可以减轻铅诱导小鼠引起的脂质过氧化和炎症反应，对小鼠肝和肾损伤均具有保护作用，其中柴胡多糖高剂量组对小鼠肝肾组织损伤保护作用最显著。

关键词: 柴胡多糖, 小鼠, 铅, 氧化应激, 炎症反应, 肝肾损伤

Abstract: This study aimed to investigate the effect of Bupleurum polysaccharide on lead-induced liver and kidney damage in mice. One hundred and fifty SPF male healthy Kunming mice were selected for the experiment. After two weeks of adaptive feeding, they were randomly divided into 5 groups, namely the control group, the lead treatment group, the lead treatment + Bupleurum polysaccharide low, medium and high dose groups (100, 200 and 400 mg·kg^-1). Establishment of the poisoning model:the mice drink lead water (0.5% lead acetate) every day for 4 consecutive weeks. After the modeling was completed, the test group was given Bupleurum polysaccharide once daily for 2 weeks. The lead content and body mass in the blood and tissues of mice were measured, and the antioxidant enzyme activity, Lipid peroxidation level and inflammatory factors were detected and analyzed, and the relative expression of oxidative damage and inflammatory response related factors mRNA was analyzed from the molecular level. The results showed that compared with the lead-treated group, Bupleurum polysaccharides can inhibit the decreasing body weight and the increase in the proportion of liver and kidney in lead-poisoned mice. The addition of Bupleurum polysaccharides reduced the lead concentration in the blood and tissues of mice, but the effect was no significant (P>0.05); compared with the lead-treated group, Bupleurum polysaccharide can significantly increase the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and peroxidase (CAT) activity in the liver and kidney tissues of lead-exposed mice (P<0.05), and reduce malondialdehyde (MDA) contents; Bupleurum polysaccharides can significantly reduce the lead-induced increase in alanine transferase (ALT) and aspartate transferase (AST) activities in the serum and liver tissues of mice, and the mice serum urea nitrogen (BUN) and creatinine (Scr) level decreased, and the tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO) activities in liver and kidney tissues of mice significantly decreased (P<0.05); Bupleurum polysaccharide can significantly increase the expression of Nrf2 signaling pathway, increase the mRNA levels of HO-1, Cu/Zn-SOD, Mn-SOD, CAT, and reduce the mRNA level of Keap1. In addition, Bupleurum polysaccharide can significantly reduce the increase of mRNA levels of inflammation factors (NF-κB, IL-1β and TNF-α) in lead-induced mice liver and kidney (P<0.05). The results showed that low-dose, middle-dose and high-dose of Bupleurum polysaccharides can alleviate lead-induced lipid peroxidation and inflammation in mice, and have protective effects on liver and kidney damage in mice. Among them, the most significant effect of Bupleurum polysaccharides high-dose group on liver and kidney tissue damage in mice.

Key words: Bupleurum polysaccharide, mice, lead, oxidative stress, inflammatory response, liver and kidney injury

中图分类号:

谢志明, 吴春梅, 陈少元, 王照, 王岩. 柴胡多糖通过抑制氧化应激和炎症反应减轻铅诱导小鼠肝肾损伤的研究[J]. 畜牧兽医学报, 2021, 52(9): 2660-2672.

XIE Zhiming, WU Chunmei, CHEN Shaoyuan, WANG Zhao, WANG Yan. Study on Bupleurum Polysaccharide Reduces Lead-induced Liver and Kidney Injury in Mice by Inhibiting Oxidative Stress and Inflammation[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(9): 2660-2672.

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