联用芝麻素和维生素E抑制PI3K/AKT信号通路改善自发性高血压大鼠的左室纤维化  

Inhibition of PI3K/AKT signaling pathway by sesamin and vitamin E improves left ventricular fibrosis in spontaneously hypertensive rats

作　　者：张俊秀[1] 沈媛媛 杨解人[1] 郑书国[1] 郝伟[1] ZHANG Junxiu;SHEN Yuanyuan;YANG Jieren;ZHENG Shuguo;HAO Wei(Department of Pharmacology,Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine,Wannan Medical College,Wuhu 241002,Anhui,China;Department of Clinical Pharmacy,Lu'an Second People's Hospital,Lu'an 237000,Anhui,China)

机构地区：[1]皖南医学院药理教研室,安徽芜湖241002 [2]六安市第二人民医院临床药学部,安徽六安237000

出　　处：《中国临床药理学与治疗学》2020年第11期1214-1222,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：Funded by National Natural Science Foundation of China(81600645);National Natural Science Foundation of China(81701161);The University Natural Science Research key Project of Anhui Province(KJ2015A192)。

摘　　要：目的:观察芝麻素(Ses)和维生素E(VitE)联用对自发性高血压大鼠(SHRs)左心室纤维化的影响,并探讨其可能机制。方法:14周龄雄性SHRs随机分为Ses和VitE联用组(160+10 mg·kg-1·d-1)、Ses组(160 mg·kg-1·d-1)、VitE组(10 mg·kg-1·d-1)及SHRs组,另设正常对照WKY组,每组7只,1次/d持续灌胃给药10周。采用尾袖法测定大鼠给药前和给药10周后的收缩压。末次给药后取左心室,计算脏器指数,Masson染色观察胶原沉积,分析心肌胶原容积分数(CVF),Western blot观察Ⅰ型胶原(collagenⅠ)、Ⅲ型胶原(collagenⅢ)、转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)、磷酸化蛋白激酶B(p-AKT)、蛋白激酶B(AKT)和磷酸肌醇3激酶(PI3K)蛋白的表达。结果:SHRs+Ses+VitE组的收缩压、HW/BW、LVW/HW、CVF明显下降,且下降幅度分别高于SHRs+Ses和SHRs+VitE组(P<0.01或P<0.05)。SHRs+Ses+VitE组的collagenⅠ、collagenⅢ、TGF-β1、CTGF、MMP-9、TIMP-1、p-AKT和PI3K蛋白表达明显下降,且下降幅度分别高于SHRs+Ses和SHRs+VitE组(P<0.01或P<0.05)。结论:联用芝麻素和维生素E通过抑制AKT/PI3K信号通路的激活,减少TGF-β1、CTGF、MMP-9及TIMP-1表达,从而发挥降压和改善左心室纤维化的作用。AIM: Sesamin( Ses) is one of the major lignans in sesame seeds with antihypertensive and antifibroticactivities,but its effect is weak. In this experiment,we combined vitamin E( Vit E) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hypertensive rats( SHRs),and to explore its possible mechanism.METHODS: Male SHRs were randomly divided into SHRs+Ses+Vit E group,SHRs+Ses group,SHRs+Vit E group,and SHRs model group. Wistar-Kyoto( WKY) rats were setted as a normal control group.After 10 weeks of administration, systolic blood pressure( SBP) of rats was measured by tail cuff method,and the left ventricle was taken to calculate the organ index. Collagen deposition was observed by Masson staining,and cardiac collagen volume fraction( CVF) was analyzed. Expressions of collagen Ⅰ,collagen Ⅲ, transforming growth factor-β1( TGF-β1),connective tissue growth factor( CTGF),matrix metalloproteinase-9( MMP-9),matrix metalloproteinase inhibitor-1( TIMP-1), phosphorylated protein kinase B( p-AKT), protein kinase B( AKT) and phosphoinositol 3 kinase( PI3K) were observed by Western blot. RESULTS: SBP,HW/BW,LVW/HW and CVF in SHRs+Ses+Vit E group decreased significantly,and the decrease was higher than that in SHRs +Ses and SHRs +Vit E group( P <0.01 or P<0.05). The expression of collagen Ⅰ,collagen Ⅲ,TGF-1,CTGF,MMP-9,TIMP-1,p-AKT and PI3K in SHRs + Ses + Vit E group decreased significantly,and the decrease was higher than that in SHRs+Ses and SHRs + Vit E group( P < 0.01 or P <0.05). CONCLUSION: Ses combined with Vit E can reduce the expression of TGF-1,CTGF,MMP-9 and TIMP-1 by inhibiting the activation of AKT/PI3K signaling pathway,thus exerting the effect of lowering blood pressure and improving left ventricular fibrosis.

关 键 词：芝麻素 维生素E 自发性高血压大鼠 左心室纤维化 转化生长因子Β1 结缔组织生长因子 磷酸肌醇3激酶/蛋白激酶B 

分 类 号：R965.2[医药卫生—药理学]