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氯化血根碱对亚砷酸钠致小鼠肝损伤的预防和治疗作用

Preventive and therapeutic effects of sanguinarine chloride on sodium arsenite-induced liver damage in mice

    摘要
  • 摘要:
    背景 天然产物氯化血根碱（SC）对小鼠肝脏纤维病变和肝脏急性损伤均有明显的改善作用，但其对环境污染物亚砷酸钠（SA）导致的小鼠肝损伤是否有保护作用尚未见报道。
    目的 研究SC对SA所致小鼠肝损伤的预防和治疗作用。
    方法 将140只SPF级雄性昆明小鼠随机分为预防效果研究组和治疗效果研究组，分别设立空白组（生理盐水），模型组（SA 5 mg·kg−1），阳性对照组（双环醇11.375 mg·kg−1和谷胱甘肽182 mg·kg−1），SC低、中、高剂量组（25、50、100 mg·kg−1），每组10只。预防效果研究中，空白组给予生理盐水，模型组给予SA，其余各组（即SC低、中、高剂量组以及阳性对照组）在SA灌胃前30 min给予相应药物，每日1次，持续处理28 d。在治疗效果研究中，空白组持续给予生理盐水；其余各组给予SA持续染毒28 d后，模型组给予生理盐水，余组每天给予相应药物进行治疗28 d。实验结束后处死小鼠，分别测定血清及其肝组织的生理生化指标，并采用HE染色观察其组织病理变化。
    结果 预防和治疗效果研究中：与空白组比较，SC各剂量组小鼠体重、肝脏质量、肝脏系数及血清谷丙转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBIL）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH）、超氧化物歧化酶（SOD）差异均无统计学意义（P＞0.05）；而与模型组比较，SC各剂量组小鼠体重上升（P<0.01），肝脏质量、肝脏系数下降（P<0.01），ALT、AST、TBIL、MDA降低（P<0.05或P<0.01），而GSH、SOD上升（P<0.05或P<0.01）或呈现上升的趋势；与阳性对照组比较，各指标差异均无统计学意义（P＞0.05）；组织病理学分析显示，SC各剂量组小鼠肝小叶结构均较清楚，肝索排列较整齐，炎症细胞浸润减少。
    结论 对SA导致的小鼠肝损伤，SC具有一定的预防和治疗效果。

     

    Abstract:
    Background Natural product sanguinarine chloride (SC) can significantly alleviate liver fibrosis and acute liver injury in mice, but whether it has a protective effect on mouse liver injury caused by sodium arsenite (SA) has not been studied.
    Objective To verify if SC may present preventive and therapeutic effects on SA-induced liver injury in mice.
    Methods A total of 140 SPF male Kunming mice were randomly divided into two sub-studies, which included a prevention sub-study and a treatment sub-study. In each sub-study, a blank group (normal saline), a model group (5 mg·kg−1 SA), and a positive control group (11.375 mg·kg−1 bicyclol and 182 mg·kg−1 glutathione), as well as SC low, medium, and high dose groups (25, 50, and 100 mg·kg−1) were arranged with 10 mice in each group. In the prevention sub-study, the blank group was given normal saline, the model group was given SA, and the other groups (the SC low, medium, and high dose groups and the positive control group) were given the corresponding treatment 30 min before gavage of SA, once a day, for 28 d. In the treatment sub-study, except for the blank group which was given normal saline, the other groups were given SA for 28 d, then the model group was given normal saline, and the other groups were given the corresponding treatment every day for 28 d. After the experiment, the mice were sacrificed to evaluate selected physiological and biochemical indicators in serum and liver tissue and to observe histopathological changes after HE staining.
    Results In either sub-study of preventive effect or treatment effect: compared with the blank group, body weight, liver weight, liver coefficient, as well as serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), malondialdehyde (MDA), glutathione peroxidase (GSH), and superoxide dismutase (SOD) among all SC groups were not significantly different (P>0.05); but compared with the model group, the SC groups showed increased body weight (P<0.01), decreased liver weight and liver coefficient (P<0.01), reduced ALT, AST, TBIL, and MDA (P<0.05 or P<0.01), and increased GSH and SOD with (P<0.05 or P<0.01) or without significance; compared with the positive control group, no differences were found in the above indicators (P＞0.05). The result of histopathological evaluation showed that the SC groups had a clear liver lobule structure, neatly arranged hepatic cords, and less infiltration of inflammatory cells.
    Conclusion SC has both preventive and therapeutic effects on SA-induced liver injury in mice.

     

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