首页|柴胡多糖对急性肝损伤小鼠的保护作用及机制研究

柴胡多糖对急性肝损伤小鼠的保护作用及机制研究

Study on protective effect and mechanism of Bupleurum chinense polysaccharides on acute liver injury in mice

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目的 研究柴胡多糖对急性肝损伤(ALI)小鼠的保护作用及机制.方法 将40只小鼠按体重随机分为正常组、模型组、阳性对照组(护肝片,550 mg/kg)和柴胡多糖高、低剂量组(400、100 mg/kg),每组8只,每天灌胃给药1次,连续7 d.末次给药1 h后,除正常组外,其余各组小鼠均尾静脉注射20 mg/kg刀豆蛋白A溶液建立ALI模型.注射刀豆蛋白A溶液12 h后,测定小鼠肝脾指数,观察其肝脾组织病理学变化;检测小鼠血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH),肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)水平;检测小鼠血清和肝组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β水平以及肝组织中核因子κB(NF-κB)、Toll样受体4(TLR4)、核转录因子红系2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的蛋白表达水平.结果 与正常组比较,模型组小鼠肝组织大量坏死、炎症细胞浸润,脾脏增大、出血增多、淋巴细胞减少,肝脾指数均显著升高(P<0.01);血清中AST、ALT、LDH水平,血清和肝组织中TNF-α、IL-6、IL-1β水平,肝组织中MDA水平和TLR4、NF-κB、HO-1蛋白表达水平均显著升高(P<0.05或P<0.01);肝组织中SOD水平和Nrf2蛋白表达水平均显著降低(P<0.05).与模型组比较,柴胡多糖高、低剂量组小鼠肝脾组织病理损伤减轻,肝脾指数、血清和肝组织中上述指标水平大部分被显著逆转(P<0.05或P<0.01).结论 柴胡多糖对ALI小鼠具有保护作用,其作用机制可能与抑制TLR4/NF-κB信号通路和激活Nrf2/HO-1信号通路有关.
OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides(BCP)on acute liver injury(ALI)in mice.METHODS Overall 40 mice were randomly divided into normal group,model group,positive control group(Baogan tablet,550 mg/kg),BCP high-dose and low-dose groups(400,100 mg/kg),with 8 mice in each group.The drug was administered intragastrical once a day for 7 days.One hour after the last administration,except for the normal group,mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model.After injection of concanavalin A solution for 12 h,the liver and spleen indexes of mice were measured,and the pathological changes of liver and spleen tissue were observed;the serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)were detected,and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue were detected.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in serum and liver tissue of mice were determined,as well as the protein expression levels of nuclear factor-κB(NF-κB),Toll-like receptor 4(TLR4),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in liver tissue were also detected.RESULTS Compared with the normal group,the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells;spleen enlargement,increased bleeding and decreased lymphocytes were observed,liver and spleen indexes were increased significantly(P<0.01);the serum levels of AST,ALT and LDH,the levels of TNF-α,IL-6 and IL-1β in serum and liver tissue,as well as the MDA level,protein expressions of TLR4,NF-κB and HO-1 in liver tissue were all increased significantly(P<0.05 or P<0.01).The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly(P<0.05).Compared with the model group,the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups,and most of liver and spleen indexes,the above indexes of serum and liver tissue were reversed significantly(P<0.05 or P<0.01).CONCLUSIONS BCP has a protective effect on ALI,the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Bupleurum chinense polysaccharidesacute liver injuryTLR4/NF-κB signaling pathwayNrf2/HO-1 signaling pathway

陈雨婵、彭东辉、孙延平、王秋红、匡海学

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黑龙江中医药大学教育部北药基础与应用研究重点实验室,哈尔滨 150040

广东药科大学中药学院,广州 510006

柴胡多糖 急性肝损伤 TLR4/NF-κB信号通路 Nrf2/HO-1信号通路

国家中医药管理局中医药传承与创新"百千万"人才工程——岐黄工程首席科学家项目国家中医药管理局中医药传承与创新"百千万"人才工程(岐黄工程)岐黄学者支持项目黑龙江省"头雁"团队支持项目

国中医药人教函[2021]7号国中医药人教函[2018]284号[2019]5号

2024

中国药房
中国医院协会,中国药房杂志社

中国药房

CSTPCD北大核心
影响因子:0.956
ISSN:1001-0408
年,卷(期):2024.35(19)
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