柴胡多糖对急性肝损伤小鼠的保护作用及机制研究
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篇名: 柴胡多糖对急性肝损伤小鼠的保护作用及机制研究
TITLE: Study on protective effect and mechanism of Bupleurum chinense polysaccharides on acute liver injury in mice
摘要: 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,550mg/kg)和柴胡多糖高、低剂量组(400、100mg/kg),每组8只,每天灌胃给药1次,连续7d。末次给药1h后,除正常组外,其余各组小鼠均尾静脉注射20mg/kg刀豆蛋白A溶液建立ALI模型。注射刀豆蛋白A溶液12h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。
ABSTRACT: 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.
期刊: 2024年第35卷第19期
作者: 陈雨婵;彭东辉;孙延平;王秋红;匡海学
AUTHORS: CHEN Yuchan,PENG Donghui,SUN Yanping,WANG Qiuhong,KUANG Haixue
关键字: 柴胡多糖;急性肝损伤;TLR4/NF-κB信号通路;Nrf2/HO-1信号通路
KEYWORDS: Bupleurum chinense polysaccharides; acute liver injury; TLR4/NF-κB signaling pathway; Nrf2/HO-1 signaling
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