隐丹参酮治疗小鼠非酒精性脂肪性肝病效果及机制研究  

Effect and mechanism of cryptotanshinone on nonalcoholic fatty liver disease in mice

作　　者：赵梦溪 罗斌 吕建瑞[1] 王宁[1] ZHAO Mengxi;LUO Bin;LYU Jianrui;WANG Ning(The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院,陕西西安710004

出　　处：《陕西医学杂志》2023年第9期1135-1139,1144,共6页Shaanxi Medical Journal

基　　金：陕西省重点研发计划项目(2022SF-038)。

摘　　要：目的:探讨隐丹参酮对小鼠非酒精性脂肪性肝病的治疗效果及相关机制。方法:将雄性C57BL/6J小鼠随机分为正常组、模型组以及隐丹参酮低、中和高剂量组,每组10只。造模8周干预4周后,采集小鼠血液检测谷丙转氨酶(ALT)和谷草转氨酶(AST);行组织病理学染色观察小鼠肝脏组织;检测肝脏组织总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和IL-6等指标。Western blot法检测肉碱棕榈酰转移酶1(CPT1)、酰基辅酶A氧化酶1(ACOX1)以及过氧化物酶体增殖物激活受体α(PPARα)蛋白表达水平。结果:肝脏组织病理染色结果显示,正常组几乎无脂肪浸润,模型组小鼠肝脏组织存在大量脂肪空泡,隐丹参酮低、中和高剂量组较模型组肝脏组织病变明显改善。与正常组比较,模型组AST、ALT、TC、TG、LDL-C、TNF-α、IL-1β、IL-6、MDA水平升高,HDL-C、SOD、GSH水平降低(均P<0.05)。与模型组比较,隐丹参酮低、中和高剂量组ALT、AST、TC、TG、LDL-C、TNF-α、IL-1β、IL-6、MDA水平降低,HDL-C、SOD、GSH水平升高(均P<0.05)。与正常组比较,模型组PPARα、CPT1和ACOX1蛋白表达水平降低(均P<0.05)。与模型组比较,隐丹参酮低、中和高剂量组PPARα、CPT1和ACOX1蛋白表达水平升高(均P<0.05)。结论:隐丹参酮对NAFLD具有治疗作用,能够改善脂质代谢,促进肝脏脂质排出,改善肝功能和减少肝脏脂质沉积,其机制可能与调节脂肪酸β-氧化、减轻炎症反应及平衡氧化应激有关。Objective:To investigate the therapeutic effect of cryptotanshinone on nonalcoholic fatty liver disease in mice and its mechanism.Methods:The C57BL/6J mice(males)were divided randomly into normal group,model group and cryptotanshinone low-,medium-and high-dose group,10 mice in each group.After 8 weeks of modeling and 4 weeks of intervention,blood samples were collected to detect ALT and AST.Their liver was collected for liver histopathology.Meanwhile,TC,TG,HDL-C,LDL-C,MDA,GSH,SOD,TNF-α,IL-1βand IL-6 in the liver were detected.Finally,Western blot was used to detected the expression characteristics of peroxisome proliferator-activated receptorα(PPARα),carnitine palmitoyl transferase 1(CPT1)and acyl CoA oxidase 1(ACOX1).Results:The results of pathological staining of liver tissue showed that there was almost no fatty infiltration in normal group,and there were a lot of fatty vacuoles in the liver tissue of model group;compared with model group,the cryptotanshinone low-,medium-and high-dose groups had significantly improved liver tissue lesions.Compared with normal group,the levels of AST,ALT,TC,TG,LDL-C,TNF-α,IL-1β,IL-6 and MDA were increased,and the levels of HDL-C,SOD and GSH were decreased in model group(all P<0.05).Compared with model group,the levels of ALT,AST,TC,TG,LDL-C,TNF-α,IL-1β,IL-6 and MDA were decreased,and the levels of HDL-C,SOD and GSH were increased in cryptotanshinone low-,medium-and high-dose groups(all P<0.05).Compared with normal group,the protein expression levels of PPARα,CPT1 and ACOX1 in model group were decreased(all P<0.05).Compared with model group,the protein expression levels of PPARα,CPT1 and ACOX1 were increased in cryptotanshinone low-,medium-and high-dose groups(all P<0.05).Conclusion:Cryptotanshinone has therapeutic effects on NAFLD,which can improve lipid metabolism,promote liver lipid excretion,improve liver function and reduce liver lipid deposition.The mechanism may be related to regulating fatty acidβ-oxidation,reducing inflammatory response and balancing oxidativ

关 键 词：非酒精性脂肪性肝病 隐丹参酮 脂肪酸β-氧化 脂质代谢 氧化应激 炎症反应 

分 类 号：R575.5[医药卫生—消化系统]