丹栀逍遥散对D-氨基半乳糖/脂多糖诱导的大鼠急性肝损伤保护作用机制研究*

doi:10.3969/j.issn.1672-5069.2022.02.007

摘要/Abstract

摘要： 目的探讨丹栀逍遥散对D-氨基半乳糖(D-GaIN)/脂多糖(LPS)诱导的大鼠急性肝损伤(ALI)的保护作用及其可能的作用机制。方法将110只SD大鼠随机分为对照组、模型组、小剂量、中剂量和大剂量丹栀逍遥散干预组,每组22只。采用D-GaIN)/LPS腹腔注射建立ALI模型,分别给予生理盐水或药物灌胃干预。采用ELISA法检测血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽-过氧化物酶(GSH-PX)、白介素-6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)水平,采用放射免疫分析法检测血清透明质酸酶(HA)、层黏连蛋白(LN)和Ⅲ型前胶原(Ⅲ-PC)水平。结果模型组血清AST、ALT、TBIL和MDA水平分别为(12081.3±587.7)U/L、(7658.7±742.2)U/L、(104.3±10.3)μmol/L和(8.9±1.1)mmol/mL,显著高于对照组【分别为(171.9±17.2)U/L、(60.5±6.2)U/L、(2.4±0.2)μmol/L 和(2.5±0.3)mmol/mL, P＜0.05】;模型组血清SOD和GSH-PX水平分别为(14.3±1.7)U/mL和(7.1±0.7)μmol/L,显著低于对照组【分别为(38.6±4.4)U/mL和(21.9±2.2)μmol/L】,而各剂量药物干预组血清SOD和GSH-PX水平显著高于模型组(P＜0.05);模型组血清IL-6、IL-1β和TNF-α水平分别为(194.3±20.5)ng/mL、(24.7±2.5)ng/ml和(864.5±87.3)ng/mL,显著高于对照组【分别为(90.1±10.3)ng/mL、(5.2±1.0)ng/mL和(30.2±4.1)ng/mL】,而各剂量药物干预组血清细胞因子水平显著低于模型组(P＜0.05);模型组血清HA、LN、Ⅲ-PC分别为(286.3±29.1)ng/ml、(297.4±30.5)ng/ml、(257.1±26.7)ng/ml,显著高于对照组【分别为(55.1±6.2)ng/mL、(75.1±7.6)ng/mL、(61.9±6.2)ng/mL】,而各剂量药物干预组血清肝纤维化指标水平显著低于模型组(P＜0.05)。结论丹栀逍遥散对D-GaIN/LPS诱导的ALI大鼠肝功能损伤有保护作用,可能与其可明显抑制机体氧化应激反应和炎症反应有关。

关键词: 急性肝损伤, 丹栀逍遥散, 氨基半乳糖, 脂多糖, 大鼠

Abstract: Objective The aim of this study was to explore the protective mechanism of Danzhi Xiaoyao powder on hepatic damage in rats with D-galactosamine (D-GaIN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI). Methods 110 SD male rats were randomly divided into control, model, low-dose, moderate dose and large-dose of herbal medicine-intervened groups, with 22 rats in each. The ALI model was built-up by D-GaIN/LPS injection intraperitoneally, and the herbal medicine was given by lavage. Serum MDA, SOD, GSH-PX, IL-6, IL-1β, TNF-α levels were detected by ELISA, and serum HA, LN and Ⅲ-PC levels were assayed by RIA. Results Serum AST, ALT, bilirubin and MDA levels in model group were (12081.3±587.7)U/L, (7658.7±742.2)U/L, (104.3±10.3)μmol/L and (8.9±1.1)mmol/mL, all significantly higher than [(171.9±17.2)U/L, (60.5±6.2)U/L, (2.4±0.2)μmol/L and (2.5±0.3)mmol/mL, respectively, P＜0.05] in the control; serum SOD and GSH-PX levels were (14.3±1.7)U/mL and (7.1±0.7)μmol/L, both significantly lower than [(38.6±4.4)U/mL and (21.9±2.2)μmol/L, P＜0.05] in the control, while serum SOD and GSH-PX levels in three herbal medicine-intervened groups significantly higher than those in the model (P＜0.05); serum IL-6, IL-1β and TNF-α levels in the model were (194.3±20.5)ng/mL, (24.7±2.5)ng/ml and (864.5±87.3)ng/mL, significantly higher than [(90.1±10.3)ng/mL, (5.2±1.0)ng/mL and (30.2±4.1)ng/mL in the control, while all significantly decreased compared to those in the model in three herbal medicine-intervened groups (P＜0.05); serum HA, LN and Ⅲ-PC levels were (286.3±29.1)ng/ml, (297.4±30.5)ng/ml and (257.1±26.7)ng/ml, all significantly higher than [(55.1±6.2)ng/mL, (75.1±7.6)ng/mL and (61.9±6.2)ng/mL] in the control, while all significantly decreased compared to those in the model in three-herbal medicine-intervened groups(P＜0.05). Conclusion Danzhi Xiaoyao powder could exert significant protective effect on liver functions in rats with D-GaIN/LPS-induced ALI, and the mechanism by which it works might be related to obvious inhibition of oxidative stress and inflammation response.

Key words: Acute liver injury, Danzhi Xiaoyao powder, herbal medicine, Galactosamine, Lipopolysaccharide, Rats

刘尚智, 张志强, 李昇锦. 丹栀逍遥散对D-氨基半乳糖/脂多糖诱导的大鼠急性肝损伤保护作用机制研究^*[J]. 实用肝脏病杂志, 2022, 25(2): 179-182.

Liu Shangzhi, Zhang Zhiqiang, Li Shengjin. Protective mechanism of Danzhi Xiaoyao powder on hepatic damage in rats with D-galactosamine/lipopolysaccharides-induced acute liver injury[J]. Journal of Practical Hepatology, 2022, 25(2): 179-182.

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丹栀逍遥散对D-氨基半乳糖/脂多糖诱导的大鼠急性肝损伤保护作用机制研究^*

Protective mechanism of Danzhi Xiaoyao powder on hepatic damage in rats with D-galactosamine/lipopolysaccharides-induced acute liver injury

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