| 七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价 |
| 投稿时间：2024-04-30 修订日期：2024-07-07 点此下载全文 |
| 引用本文：杨嘉宁,赵一颖,肖伟.七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价[J].药学实践杂志,2024,42(9):389~398 |
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| 基金项目:[基金项目] 江苏省科学技术厅基础研究计划自然科学基金——前沿引领技术基础研究专项（SBK2023050003） |
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| 中文摘要:目的 探讨七味脂肝方对两种经典的非酒精性脂肪性肝炎（NASH）动物模型的药效作用。方法 采用蛋氨酸-胆碱缺乏（MCD）饲料饮食诱导大鼠模型和胆碱缺乏的高脂饮食（CDAHFHC）诱导小鼠非酒精性脂肪性肝炎模型，将48只大鼠和96只小鼠均随机分为6组：对照组、模型组、七味脂肝方组（低、中、高剂量组）、阳性药组，造模2周后，连续干预28 d。通过检测各组动物血清肝功能、血脂生化指标以及肝组织脂质水平，并进行肝脏组织病理学评价，以评估七味脂肝方治疗非酒精性脂肪性肝炎的药效作用。结果 七味脂肝方以临床等效剂量及以上剂量在两种试验动物模型灌胃给药后，能改善肝脏大体解剖形态，降低NASH小鼠肝脏重量及肝脏指数；降低NASH大鼠血清ALT、ALP、LDH，升高HDL水平；降低NASH小鼠血清ALT、AST、TBIL、ALP、LDH及TG水平，并降低肝脏TG含量。其还可改善肝脏组织病理损伤，减轻肝脏组织炎症程度，减轻肝细胞气球样变程度，降低肝脏NAS评分，且各剂量组间呈一定量效关系趋势；有效减轻NASH小鼠肝小叶内和汇管区周围胶原纤维增生情况；降低被F4/80标记的阳性细胞数密度，减轻Kupffer细胞活化程度。结论 七味脂肝方可有效改善两种经典NASH模型的进展程度，改善NASH肝脏炎症损伤向肝纤维化发展的趋势。 |
| 中文关键词:中医药 七味脂肝方 非酒精性脂肪性肝炎 蛋氨酸-胆碱缺乏 胆碱缺乏 |
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| Pharmacodynamic effects of Qiwei Zhigan prescription on non-alcoholic steatohepatitis in animal model |
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| Abstract:Objective To investigate the therapeutic effect of Qiwei Zhigan prescription on two classic animal models of non-alcoholic steatohepatitis（NASH）. Methods Methionine-choline-deficient（MCD）rat model and choline-deficient, L-amino acid-defined, high-fat and high cholesterol diet（CDAHFHC）mouse model were used. 48 rats and 96 mice were randomly divided into 6 groups: control group, model group, Qiwei Zhigan prescription group（low, medium and high dose group）, positive drug group. After 2 weeks of modeling, the drugs were administrated continuously for 28 days. The efficacy of Qiwei Zhigan prescription in the treatment of non-alcoholic steatohepatitis was evaluated by detecting the serum liver function, blood lipid biochemical index and liver tissue lipid levels of each group of animals, as well as by evaluating the liver histopathological changes. Results The gross anatomical morphology of the liver was improved by Qiwei Zhigan after oral administration of clinical equivalent dose or higher doses in two experimental animal models. The liver weight and liver index of NASH mice were reduced by the prescription. The levels of ALT, ALP and LDH in serum of NASH rats were decreased, and the level of HDL was increased. The levels of ALT, AST, TBIL, ALP, LDH and TG in serum of NASH mice were decreased, and the content of TG in liver was also decreased. The pathological damage of liver tissue was ameliorated, the inflammation of liver tissue was reduced, as well as the degree of ballooning of liver cells and the NAS score of the liver, and there was a certain dose-effect relationship between the groups; the proliferation of collagen fibers in the hepatic lobules and around the portal area of NASH mice was significantly reduced; the density of positive cells labeled by F4/80 was decreased, and the activation of Kupffer cells was alleviated. Conclusion Qiwei Zhigan prescription could effectively ameliorate the progression of two classic NASH models, and decrease the development trend from liver inflammation to liver fibrosis in NASH. |
| keywords:traditional Chinese medicine Qiwei Zhigan prescription non-alcoholic steatohepatitis methionine-choline deficiency choline deficiency |
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