丹酚酸B通过抑制MAPKs/NF-κB信号通路减轻动脉粥样硬化模型小鼠肝脏炎症反应  

Salvianolic acid B reduces liver inflammation in mice with atherosclerosis by inhibiting MAPKs/NF-κB signaling pathway

作　　者：张一凡 韩向晖 刘萍[1] ZHANG Yi-fan;HAN Xiang-hui;LIU Ping(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Institute of Traditional Chinese Medicine Surgery,Shanghai 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 [2]上海中医药大学中医外科研究所,上海200032

出　　处：《中国药理学通报》2022年第4期525-530,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81873117)。

摘　　要：目的探究丹酚酸B(salvianolic acid B,Sal B)对动脉粥样硬化模型小鼠肝脏炎症反应的影响及其作用机制。方法将32只♂LDLR-/-小鼠随机分为对照组、模型组、Sal B组、阿托伐他汀组。对照组给予普通饲料喂养,其余各组给予高脂饲料喂养12周。对照组、模型组生理盐水腹腔注射,Sal B组予以Sal B溶液腹腔注射,阿托伐他汀组以阿托伐他汀溶液灌胃12周。采用生化检测方法检测小鼠血清TC、TG、AST、ALT值。油红O染色观察小鼠主动脉窦斑块面积,HE染色法观察小鼠肝脏病理改变。RT-PCR、ELISA法检测IL-1β、IL-6、TNF-αmRNA及含量,蛋白质印迹法测定小鼠肝组织VCAM、iNOS、JNK、p38、ERK1/2、IκB、NF-κB蛋白表达。结果与模型组比较,Sal B、阿托伐他汀降低小鼠血清TC、TG、AST、ALT水平(P<0.05),减小小鼠主动脉斑块面积,改善肝组织病理变化,下调小鼠IL-1β、IL-6、TNF-αmRNA及含量(P<0.05),降低小鼠肝组织VCAM、iNOS蛋白水平,以及JNK、p38、ERK1/2、IκB、NF-κB蛋白磷酸化水平(P<0.05)。结论Sal B减轻动脉粥样硬化模型小鼠肝脏炎症反应,该作用可能与其抑制MAPKs/NF-κB信号通路相关。Aim To explore the effect of salvianolic acid B on liver inflammation in atherosclerosis model mice and its mechanism.Methods Thirty-two male LDLR-/-mice were randomly divided into control group,model group,salvianolic acid B group,and atorvastatin group.The control group was fed with ordinary feed,and the other groups were fed with high-fat feed for 12 weeks.The control group and the model group were injected intraperitoneally with normal saline,the salvianolic acid B group was injected intraperitoneally with the salvianolic acid B solution,and the atorvastatin group was given intragastrically with atorvastatin solution for 12 weeks.Biochemical detection methods were used to detect the serum TC,TG,AST and ALT values of mice.Oil red O staining was used to observe mouse aortic sinus plaque area,and HE staining was used to observe pathological changes of mouse liver.ELISA and RT-PCR methods were used to detect serum IL-1β,IL-6,and TNF-αlevels,and IL-1β,IL-6,and TNF-αmRNA in liver.Western blot was used to determine the protein expression of VCAM,iNOS,JNK,p38,ERK1/2,IκB,and NF-κB in mouse liver tissues.Results Compared with model group,salvianolic acid B and atorvastatin reduced the levels of serum TC,TG,AST,and ALT in mice(P<0.05),reduced the plaque area of aorta in mice,and improved the pathological changes of liver tissues,and down-regulated mouse serum IL-1β,IL-6,TNF-αcontent and mRNA levels(P<0.05).Salvianolic acid B reduced the protein levels of VCAM and iNOS in liver tissues of mice,as well as the phosphorylation levels of JNK,p38,ERK1/2,IκB,and NF-κB proteins(P<0.05).Conclusions Salvianolic acid B reduces liver inflammation in atherosclerotic model mice,which may be related to its inhibition of MAPKs/NF-κB signaling pathway.

关 键 词：丹酚酸B 动脉粥样硬化 肝脏 炎症反应 MAPKs/NF-κB信号通路 LDLR^(-/-)小鼠 

分 类 号：R-332[医药卫生] R284.1