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Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease
- ZHONGGUO YAOFANG Vol. 35, Issue 11, Pages: 1345-1350(2024)
- 作者机构：
1.青岛大学附属青岛市海慈医院（青岛市中医医院）影像科，山东 青岛;266031
2.青岛市中心医院神经内科，山东 青岛 266042
3.青岛大学附属青岛市海慈医院（青岛市中医医院）消化内科，山东 青岛 266031
4.陇南市武都区中心医院内科，甘肃 陇南 742500
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.11.11
CLC： R965;R285.5Published：15 June 2024，
Received：22 November 2023，
Revised：18 March 2024，
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王燕,陈翠青,徐岩等.五味保肝丸对非酒精性脂肪性肝病小鼠的干预作用及机制 Δ[J].中国药房,2024,35(11):1345-1350.
WANG Yan,CHEN Cuiqing,XU Yan,et al.Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease[J].ZHONGGUO YAOFANG,2024,35(11):1345-1350.
王燕,陈翠青,徐岩等.五味保肝丸对非酒精性脂肪性肝病小鼠的干预作用及机制 Δ[J].中国药房,2024,35(11):1345-1350. DOI： 10.6039/j.issn.1001-0408.2024.11.11.
WANG Yan,CHEN Cuiqing,XU Yan,et al.Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease[J].ZHONGGUO YAOFANG,2024,35(11):1345-1350. DOI： 10.6039/j.issn.1001-0408.2024.11.11.
摘要
目的
2
考察五味保肝丸对非酒精性脂肪性肝病（NAFLD）小鼠的干预作用及机制。
方法
2
采用高脂高糖饲料持续喂养小鼠19周复制NAFLD模型。将造模成功的小鼠分为模型组、阳性对照组（多烯磷脂酰胆碱胶囊，23.30 mg/kg）和五味保肝丸低、中、高剂量组（0.11、0.23、0.45 g/kg），另设不造模的正常组，每组8只。药物组小鼠灌胃相应药物，模型组和正常组小鼠灌胃等体积生理盐水，每天1次，连续4周。末次给药结束后，检测各组小鼠的糖代谢（空腹血糖、空腹胰岛素、胰岛素抵抗指数）、肝功能[肝指数、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肝组织病理评分]、脂代谢[甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]相关指标；观察肝组织病理学形态以及纤维化、脂滴形成和糖原合成情况；检测血清中游离脂肪酸（FFA）和肝组织中炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β]水平；检测肝组织中胰岛素受体底物/磷脂酰肌醇3-激酶/蛋白激酶B/糖原合成酶激酶3β（IRS/PI3K/AKT/GSK3β）信号通路相关蛋白表达水平。
结果
2
经高剂量的五味保肝丸干预后，NAFLD小鼠肝指数，血清中ALT、AST、FFA、TC、TG、LDL-C水平，肝组织中TNF-α、IL-6、IL-1β水平，空腹血糖、空腹胰岛素、胰岛素抵抗指数，肝组织病理评分、纤维化染色面积占比、脂滴染色面积占比均显著降低（
P
＜0.05）；HDL-C水平、糖原染色面积占比和肝组织中IRS1、PI3K、AKT、GSK3β蛋白磷酸化水平均显著升高（
P
＜0.05）；肝细胞坏死和脂肪变性程度均减弱，纤维化病变均减轻。五味保肝丸低、中剂量组小鼠的上述指标均有改善趋势，但部分差异无统计学意义。
结论
2
五味保肝丸可调节NAFLD小鼠肝脏脂代谢、糖代谢紊乱，改善肝损伤，其作用机制可能与激活IRS/PI3K/AKT/GSK3β信号通路有关。
Abstract
OBJECTIVE
2
To investigate the intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease （NAFLD）.
METHODS
2
The mice were given high-fat and high-sugar diet for 19 weeks to induce NAFLD model. The model mice were randomly grouped into model group， positive control group （polyene phosphatidylcholine capsules， 23.30 mg/kg）， Wuwei baogan pill low-dose， medium-dose and high-dose groups （0.11， 0.23， 0.45 g/kg）， with 8 mice in each group； the normal group was additionally set up without modeling. Administration groups were given relevant medicine intragastrically， and model group and normal group were given constant volume of normal saline， once a day， for consecutive 4 weeks. After the last administration， glucose metabolism （including fasting blood glucose， fasting insulin， insulin resistance index）， liver function [liver index， alanine aminotransferase （ALT）， aspartate aminotransferase （AST），liver tissue pathological score]， lipid metabolism [triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）] were measured； the pathological morphology of liver tissue， as well as fibrosis， lipid droplet formation， and glycogen synthesis were observed； the levels of free fatty acid （FFA） in serum and inflammatory factors in liver tissue [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β] were detected； the expressions of insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B/ glycogen synthase kinase 3β （IRS/PI3K/AKT/GSK3β） signaling pathway-related protein in liver tissue were investigated.
RESULTS
2
After intervention with high-dose Wuwei baogan pill， liver index of NAFLD mice， serum levels of ALT， AST， FFA， TC， TG and LDL-C， the levels of TNF-α， IL-6 and IL-1β in liver tissue， fasting blood glucose， fasting insulin， insulin resistance index， liver tissue pathological score， proportions of fibrotic staining area and lipid droplet staining area all significantly decreased （
P
＜0.05）； the level of HDL-C， proportion of glycogen staining area， the phosphorylation of IRS1， PI3K， AKT and GSK3β protein increased significantly （
P
＜0.05）； the degree of liver cell necrosis and steatosis was reduced， and the fibrotic lesions were alleviated. The above indexes of mice were improved in Wuwei baogan pill low-dose and medium-dose groups， but there was no statistically significant difference in some indexes.
CONCLUSIONS
2
Wuwei baogan pill can regulate lipid and glucose metabolism disorders in the liver of NAFLD mice， and improve liver injury， the mechanism of which may be associated with the activation of IRS/PI3K/AKT/GSK3β signaling pathway.
关键词
五味保肝丸非酒精性脂肪性肝病脂代谢糖代谢炎症因子肝损伤IRS/PI3K/AKT/GSK3β信号通路
Keywords
non-alcoholic fatty liver diseaselipid metabolismglucose metabolisminflammatory factorsliver injuryIRS/PI3K/AKT/GSK3β signaling pathway
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