冠心康通过肝胞葬作用改善LDLR^(-/-)动脉粥样硬化模型小鼠肝脏脂肪变性的机制研究  

Mechanism of Guanxinkang ameliorating hepatic steatosis by liver efferocytosis in LDLR^(-/-)atherosclerosis model mice

作　　者：王佳柔 冯骁腾 杜敏 张一凡 李斯锦 常鑫迪 刘萍[1] WANG Jia-rou;FENG Xiao-teng;DU Min;ZHANG Yi-fan;LI Si-jin;CHANG Xin-di;LIU Ping(Longhua Hospital Shanghai of University of Traditional Chinese Medicine,Shanghai,200032,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032

出　　处：《时珍国医国药》2024年第5期1029-1033,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81873117)。

摘　　要：目的通过观察冠心康对肝胞葬作用的影响,探讨冠心康改善LDLR^(-/-)动脉粥样硬化(atherosclerosis,AS)模型小鼠肝脏脂肪变性的可能机制。方法选取LDLR^(-/-)小鼠西方饮食制备AS模型,随机分为模型组、冠心康组和阿托伐他汀组,另取C57BL/6J小鼠作为对照组。干预结束后,检测血清天门冬氨酸氨基转移酶(Aspartate Aminotransferase,ALT)、谷草转氨酶(Aspartate Transaminase,AST)、总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)含量;HE和油红O染色观察主动脉和肝组织病理变化;RT-qPCR和Western blot法分别检测肝脏1-磷酸-鞘氨醇受体1(Sphingosine-1-phosphate,S1P1)、趋化因子受体1(Chemokine C-X3-C-Motif Receptor 1,CX3CR1)、酪氨酸激酶(MER proto-oncogene tyrosine kinase,MERTK)、乳脂球表皮生长因子8(Recombinant Milk Fat Globule EGF Factor 8,MFGE8)mRNA和蛋白相对表达量;免疫荧光法检测肝脏胞葬信号和凋亡细胞表达。结果与对照组相比,模型组小鼠主动脉窦斑块明显增大(P<0.01),血清ALT、AST、TC、TG水平显著升高(P<0.01),肝组织可见病理变化和脂肪样变性,肝脏S1P1、CX3CR1、MERTK、MFGE8 mRNA和蛋白相对表达量显著降低(P<0.01),S1P1信号表达减弱(P<0.05)、Caspase-3(P<0.01)信号表达增强;与模型组相比,冠心康及阿托伐他汀组小鼠主动脉窦斑块明显减小(P<0.01),冠心康组小鼠血清ALT、AST、TC、TG水平显著降低(P<0.01),肝组织病理改变及脂肪样变性好转,S1P1、CX3CR1、MERTK、MFGE8mRNA和蛋白相对表达量显著升高(P<0.01),S1P1信号表达增强(P<0.01)、Caspase-3信号表达减弱(P<0.01);结论冠心康可能通过促进肝胞葬作用改善LDLR^(-/-)AS模型小鼠肝脏脂肪变性。Objective The research aims to observe the effect of Guanxinkang decoction on liver steatosis in LDLR^(-/-)atherosclerosis mice through liver efferocytosis.Methods Eighteen LDLR^(-/-)mice were randomly divided into model group,Guanxinkang decoction group and atorvastatin group.After 12 weeks of high-fat diet,the model group,Guanxinkang decoction group and atorvastatin group were treated with normal saline,Guanxinkang decoction 28.66g/(kg•d)and atorvastatin suspension 5mg/(kg·d)by gavage for 12 weeks,respectively.Another six C57BL/6J mice were used as the normal control group,and were fed with normal diet for 24 weeks.The levels of serum Aspartate Aminotransferase(ALT),Aspartate Transaminase(AST),total cholesterol(TC)and Triglyceride(TG)were detected by automatic biochemical analyzer;HE and oil red O staining was used to observe the pathological changes of aortic sinus and liver tissue.RT-qPCR and Western blot were used to detect liver Sphingosine-1-phosphate Receptor 1(S1P1)and Chemokine C-X3-C-Motif receptor 1(CX3CR1),MER proto-oncogene tyrosine kinase(MERTK)and Recombinant Milk Fat Globule EGF Factor 8(MFGE8)mRNA and protein relative expression.Results Compared with the control group,the serum levels of ALT,AST,TC,and TG in the model group were significantly increased(P<0.01),and pathological changes and steatosis were observed in the liver tissue.The relative expressions of S1P1,CX3CR1,MERTK,and MFGE8mRNA and protein in the liver were significantly decreased(P<0.01).Compared with the model group,the serum levels of ALT,AST,TC and TG in the Guanxinkang decoction group were significantly decreased(P<0.01),the pathological changes and steatosis of liver tissue were improved,and the relative expressions of S1P1,CX3CR1,MERTK and MFGE8mRNA and protein were significantly increased(P<0.01).Conclusion Guanxinkang decoction may improve liver steatosis in LDLR^(-/-)AS model mice by promoting liver efferocytosis.

关 键 词：冠心康 肝胞葬作用 LDLR^(-/-)小鼠 动脉粥样硬化 肝脂肪变性 

分 类 号：R285.5[医药卫生—中药学]