非酒精脂肪性肝炎合并肌少症发病机理研究  

Pathogenesis of Nonalcoholic Steatohepatitis with Sarcopenia

作　　者：王淳[1,3] 谭婉莹 赵丰娟 邓江婷 谭正怀 WANG Chun;TAN Wanying;ZHAO Fengjuan;DENG Jjangting;TAN Zhenghuai(Chengdu University of Traditional Chinese Medicine,Chengdu 610072;Southwest Medical University,Luzhou 646000;Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica,Sichuan Provincial Key Discipline of Traditional Chinese Medicine Pharmacology,Evaluation Platform of Pharmacodynamics of CM for Major Disease Prevention and Treatment,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041)

机构地区：[1]成都中医药大学,成都610072 [2]西南医科大学,泸州646000 [3]四川省中医药科学院中药材品质及创新中药研究四川省重点实验室、四川省中药药理学重点学科、财政部中药防治重大疾病药效学评价平台,成都610041

出　　处：《中药药理与临床》2024年第11期87-92,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省中央引导地方科技发展专项项目(编号:2021ZYD0088)。

摘　　要：目的:非酒精性脂肪性肝炎(NASH)合并肌少症的发病率显著升高,其相关机理至今没有得到系统阐明。本文拟通过动物模型揭示NASH与肌少症之间内在联系,为临床和新药研发提供研究工具和理论依据。方法:采用三因素两水平析因设计,以血液、肝脏及肌肉生化指标,病理组织学观察评价考察去势手术、地塞米松在小鼠肌少症形成过程中的作用。结果:切除睾丸可使小鼠肝脏和肌肉指数显著减少,僵立时间明显延长,血清TBA、TG、LDL-C及Glu含量显著升高,肝脏TG及TC含量、肌肉MDA、TG及LDH含量均显著升高(P<0.01);血清ALT和AST活力下降(P<0.05或P<0.01)。切除卵巢可使小鼠肌肉指数减少、僵立时间延长、肝脏羟脯氨酸及肌肉丙酮酸含量显著增加;长期大剂量注射地塞米松可引起小鼠肌肉指数显著减少,肌力明显减弱,血清ALT活力、TG、TC、HDL-C、LDL-C、Crea含量明显升高,肌肉TG含量以及肝脏TG、TC含量均显著升高,肝糖原含量降低(P<0.05或P<0.01);腹腔注射地塞米松可使去势小鼠发生相似的NASH伴肌少症样改变,但其肌肉乳酸含量明显降低(P<0.05)。结论:性激素降低与地塞米松在雄性动物NASH伴肌少症的形成中具有明显的协同增强效应,NASH合并肌少症是NASH的全身反应,其发生、发展与机体胰岛素抵抗、性激素水平以及蛋白质、脂质新陈代谢水平密切相关。Objective:The incidence of nonalcoholic steatohepatitis(NASH)with sarcopenia is rising,while the mechanism underlying this condition has not been systematically elucidated.This article aims to reveal the internal relationship between NASH and sarcopenia by animal models and provide research tools and a theoretical basis for clinical practice and new drug development.Methods:A three-factor two-level orthogonal design was adopted to evaluate the effects of castration and dexamethasone on the formation of sarcopenia in mice based on blood,liver,and muscle biochemical indexes and histopathological observation.Results:The mice subjected to testicular resection showcased decreased liver and muscle indexes,prolonged freezing time,elevated levels of total bile acid(TBA),triglycerides(TG),low-density lipopolysaccharide cholesterol(LDL-C),and glucose(Glu)in the serum,TG and total cholesterol(TC)in the liver,and malondialdehyde(MDA),TG,and lactate dehydrogenase(LDH)in the muscle,and lowered levels of alanine transaminase(ALT)and aspartate transaminase(AST)in the serum.Ovariectomy of mice reduced the muscle index,prolonged the freezing time,and elevated the levels of hydroxyproline in the liver and pyruvate in the muscle.Long-term injection of high-dose dexamethasone induced significant decreases in muscle index and muscle strength,elevated the levels of ALT,TG,TC,HDL-C,LDL-C,and creatine(Crea)in the serum,TG in the muscle,and TG and TC in the liver,and lowered the glycogen level in the liver.Intraperitoneal injection of dexamethasone induced changes similar to NASH with sarcopenia,while it lowered the lactic acid level in the muscle in ovariectomized mice.Conclusion:The decreases in sex hormones and dexamethasone demonstrate synergistic enhancement effect in the formation of NASH with sarcopenia in male animals.NASH with sarcopenia is a systemic reaction of NASH,and its occurrence and development are closely related to insulin resistance,sex hormone levels,and protein and lipid metabolism levels.

关 键 词：非酒精性脂肪性肝炎 地塞米松 雄激素 雌激素 肌少症 小鼠 

分 类 号：R57[医药卫生—消化系统]