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白杨素减轻非酒精性脂肪性肝炎小鼠脂肪变性及血脂异常OA北大核心CSTPCD

Chrysin attenuates hepatic steatosis and blood lipid dysregulation in a mouse model of nonalcoholic steatohepatitis

中文摘要英文摘要

目的:探究白杨素对非酒精性脂肪性肝炎(NASH)的治疗作用.方法:将8周龄C57BL/6雄性小鼠随机分为对照组、模型组和白杨素组.除对照组给予普通饲料外,其余各组给予蛋氨酸胆碱缺乏(MCD)饲料喂养.造模5周后灌胃,白杨素组给予白杨素(20 mg/kg),对照组和模型组给予同体积生理盐水,连续给药6周.实验期间观察小鼠状态;处死后观察小鼠肝脏形态;检测体质量和肝脏湿重;用生化分析仪检测血清中甘油三酯(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)含量、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平;用试剂盒检测肝脏组织中TG和TC含量;采用苏木素-伊红(HE)染色和F4/80免疫组化染色探究白杨素对NASH中肝细胞损伤和炎症的影响;用油红O染色探究肝脏脂质沉积的程度;Masson和天狼星红染色检测肝纤维化;免疫组化法检测纤维化相关分子的表达水平.结果:与对照组比较,模型组小鼠体重和肝脏湿重明显下降,肝脏体积减小,呈黄色,可见黄色脂肪斑,边缘钝;血清TG、LDL-C、ALT和AST水平,以及肝组织TG和TC水平显著升高,HDL-C水平降低;病理染色结果显示有明显的炎症细胞浸润、脂质沉积及肝脏纤维化.与模型组相比,白杨素组小鼠体重和肝重均有升高,肝脏红润,表面相对光滑,肝缘锐利;血清TG、LDL-C、AST和ALT水平,以及肝组织TG水平显著降低;白杨素可抑制炎症细胞浸润、脂质沉积及肝组织纤维化.结论:白杨素可抑制肝脏脂肪变性、炎症及纤维化,有潜力成为治疗NASH的候选药物.

AIM:To investigate the therapeutic effects of chrysin on nonalcoholic steatohepatitis(NASH).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,model group,and chrysin group.The mice in control group were fed with normal diet,and those in model and chrysin groups were fed with methio-nine-and choline-deficient(MCD)diet.After 5 weeks of adaptation,the mice in chrysin group received chrysin treatment(20 mg/kg)by continuous lavage for 6 weeks,while those in control and model groups were given equal volume of saline.During the experiment,the health condition of the mice was monitored.Liver morphology was examined after the mice were sacrificed.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-den-sity lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured using a biochemical analyzer.Liver tissue TG and TC levels were measured using assay kits.Liver cell damage and inflammation were assessed by hematoxylin-eosin(HE)staining and F4/80 immunohistochemistry staining.The ex-tent of liver lipid deposition was explored by oil red O staining.Masson staining and Sirius red staining were performed to assess liver fibrosis.Immunohistochemistry was performed to analyze the expression of fibrosis-related molecules.RE-SULTS:Compared with control group,the mice in model group showed significant decrease in body weight,liver wet weight,and liver volume.Serum TG,LDL-C,ALT and AST levels,as well as liver TG and TC levels were significantly elevated,and HDL-C levels were decreased in model group.Pathological staining showed significant inflammatory cell in-filtration,lipid deposition,and liver fibrosis.After the treatment with chrysin,increased body weight and liver weight,a reddish appearance of the liver,relatively smooth surface,and sharp liver edges were observed.Serum TG,LDL-C,AST and ALT levels,and liver TG levels were significantly reduced by chrysin.Inflammatory cell infiltration,lipid deposition,and liver tissue fibrosis were also significantly attenuated by chrysin.CONCLUSION:Chrysin shows a potential as a can-didate drug for the treatment of NASH by inhibiting hepatic steatosis,inflammation,and liver fibrosis.

王星星;李沫;高川月;熊伯成;张秀芬;李晓梅;杨细飞

山西医科大学公共卫生学院,山西 太原 030000||深圳市疾病预防控制中心深圳市现代毒理学重点实验室,深圳市卫生毒理学医学重点学科,广东 深圳 518000山西医科大学公共卫生学院,山西 太原 030000深圳市疾病预防控制中心深圳市现代毒理学重点实验室,深圳市卫生毒理学医学重点学科,广东 深圳 518000南华大学公共卫生学院,湖南 衡阳 421200暨南大学药学院,广东 广州 510632

临床医学

白杨素非酒精性脂肪性肝炎蛋氨酸胆碱缺乏饮食肝脏纤维化

chrysinnonalcoholic steatohepatitismethionine-and choline-deficient dietliver fibrosis

《中国病理生理杂志》 2024 (005)

899-907 / 9

国家自然科学基金资助项目(No.82171583);深圳市医学重点学科建设经费资助项目(No.SZXK069);深圳市科技创新委员会重点基础研究计划项目(No.JCYJ20200109150717745XY;No.JCYJ20200109144418639);深圳市医疗卫生三名工程项目(No.SZSM201611090)

10.3969/j.issn.1000-4718.2024.05.015

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