Chin J Schisto Control ›› 2019, Vol. 31 ›› Issue (6): 615-.

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Polysaccharide from Phellinus igniarius alleviates oxidative stress and hepatic fibrosis in Schistosoma japonicum?infected mice

ZHANG Jia-Ning, QU Hai-Yan, ZHANG Jin-Meng, FENG Jin-Mei, SONG Wen-Jian, YUAN Fa-Hu*   

  1. School of Medcine, Jianghan University, Wuhan 430056, China
  • Online:2020-01-17 Published:2020-01-18

桑黄多糖缓解日本血吸虫感染小鼠氧化应激及 肝纤维化的实验研究

张珈宁,瞿海燕,张金梦,冯金梅,宋文剑,袁发浒*   

  1. 江汉大学医学院(武汉 430056)
  • 作者简介:张珈宁,女,本科生。研究方向:临床医学
  • 基金资助:
    湖北省卫计委血防专项科研项目(WJ2017X16);湖北省大学生创新创业训练项目(201611072024)

Abstract: Objective To evaluate the role of polysaccharide from Phellinus igniarius (PPI) in the improvement of oxidative stress, hepatic granuloma and hepatic fibrosis in Schistosoma japonicum?infected in mice. Methods The mouse model of schistosomiasis was established by S. japonicum cercariae infection via the abdomen. Balb/c mice were randomly assigned into 5 groups, including the healthy control group (Group A), infection control group (Group B), PPI treatment group (Group C), praziquantel treatment group (Group D) and PPI?praziquantel combination group (Group E), of 10 mice in each group. Each mouse in groups B, C, D and E was infected with (30 ± 2) S. japonicum cercariae. Then, mice in groups D and E were given praziquantel by gavage at a dose of 500 mg/kg for successive two days on day 42 post?infection, while mice in groups C and E were given PPI by gavage at a dose of 400 mg/kg for successive 30 days on day 42 post?infection. Histopathological changes of hepatic tissues were observed using hematoxylin?eosin (HE) staining, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) were determined, while the activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH?PX), glutathione reductase (GSH?R) and glutathione (GSH) were detected in Mouse liver homogenates. The expression of transforming growth factor?beta (TGF?β) and alpha?smooth muscle actin (α?SMA) was quantified in hepatic tissues using immunohistochemistry, and the Nrf2 and Gsta4 gene expression was quantified using quantitative real?time PCR (qPCR) assay. Results Untreated mice presented typical pathological changes of schistosomal hepatic disorders, while PPI treatment effectively alleviated hepatic egg granulomas and collagen deposition. S. japonicum infection resulted in aggravation of hepatic lipid peroxidation, induction of oxidative stress, elevated serum MDA level and a reduction in the activity of GSH and antioxidant enzymes activities in mice. As compared to infected but untreated mice, PPI treatment suppressed hepatic lipid peroxidation, increased the GSH activity and restored the activity of antioxidant enzymes. In addition, PPI treatment inhibited the TGF?β signaling pathway and up?regulated the Nrf2 and Gsta4 gene expression. Conclusions PPI plays a critical role in the treatment of schistosomiasis?induced hepatic fibrosis. It may improve oxidative stress damages through up?regulating Nrf2 and Gsta4 gene expression, thereby suppressing the development of hepatic egg granulomas and hepatic fibrosis.

Key words: Schistosoma japonicum, Phellinus igniarius, Polysaccharide, Hepatic fibrosis, Oxidative stress

摘要: 目的 探讨桑黄醇提多糖(PPI)对日本血吸虫感染小鼠氧化应激、肝肉芽肿和肝纤维化的改善作用。方法 采用日本血吸虫尾蚴玻片贴腹感染法建立日本血吸虫肝病小鼠模型。设健康对照组(A组)、感染对照组(B组)、PPI单独治疗组(C组)、吡喹酮单独治疗组(D组)和PPI加吡喹酮混合治疗组(E组),每组各10只小鼠;除A组外,其他各组每只小鼠感染(30 ± 2)条尾蚴。自感染后42 d开始,D、E组小鼠灌胃给予500 mg/kg吡喹酮,连续2 d;C、E组给予400 mg/kg PPI灌胃,连续给药30 d。HE染色观察小鼠肝组织病理学改变,测定小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、透明质酸(HA)、层黏连蛋白(LN)及小鼠肝组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH?PX)、谷胱甘肽还原酶(GSH?R)、谷胱甘肽(GSH)含量,采用免疫组化技术检测小鼠肝组织中转化生长因子?β(TGF?β)、α?平滑肌肌动蛋白(α?SMA)表达水平,采用实时荧光定量PCR检测Nrf2、Gsta4基因表达水平。结果 日本血吸虫感染但未予治疗小鼠出现典型血吸虫病肝病病理改变,PPI干预后能有效减轻小鼠肝虫卵肉芽肿及胶原沉积。血吸虫病肝病小鼠肝脏脂质过氧化加剧,诱导了氧化应激,小鼠血清中MDA含量增加,GSH和各种抗氧化酶含量下降。与B组相比,PPI治疗抑制了脂质过氧化,提高了GSH含量,恢复了抗氧化酶活性。此外,PPI治疗可抑制TGF?β信号通路,提升Nrf2、Gsta4基因表达水平。结论 PPI在治疗血吸虫病肝纤维化方面发挥重要作用,其内在机制可能是通过上调Nrf2和Gsta4基因表达、改善氧化应激损伤,从而抑制肝脏虫卵肉芽肿形成和肝纤维化。

关键词: 日本血吸虫, 桑黄, 多糖, 肝纤维化, 氧化应激

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