玉郎伞MHBFC调控eNOS-NO信号通路逆转大鼠心室重构的机制研究  

Mechanism of Yulangsan MHBFC regulating eNOS-NO signaling pathway in reversing ventricular remodeling in rats

作　　者：叶芳杏 何俊慧 李梅兰 黄仁彬[1] 谢佳秀 黄建春[1] YE Fang-xing;HE Jun-hui;LI Mei-lan;HUANG Ren-bin;XIE Jia-xiu;HUANG Jian-chun(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《中国药理学通报》2018年第11期1516-1520,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81560587);霍英东教育基金项目(No 151107)

摘　　要：目的观察玉郎伞单体17-甲氧基-7-羟基-苯并呋喃查尔酮(MHBFC)调控心肌微血管内皮细胞(MMVEC)eNOS-NO信号通路,逆转大鼠压力超负荷心室重构的机制。方法将缩窄腹主动脉的成活大鼠随机分为假手术组、模型组、MHBFC 6 mg·kg^(-1)组、MHBFC 12 mg·kg^(-1)组、MHBFC 12 mg·kg^(-1)+亚硝基左旋精氨酸甲酯(L-NAME)50 mg·kg^(-1)组、L-NAME 50 mg·kg^(-1)组。假手术组只游离腹主动脉,不缩窄。分组后,各组给予相应药物6周。化学消化法分离左心室组织获得MMVEC;Dil-Ac-LDL吞噬实验鉴定MMVEC;qPCR检测MMVEC eNOS、PI3K和Akt基因表达;Western blot检测MMVEC p-eNOS、p-PI3K和p-Akt蛋白表达。结果 MHBFC预处理组明显上调MMVEC p-eNOS、p-PI3K、p-Akt蛋白表达,以及MMVEC eNOS、PI3K、Akt基因表达;L-NAME组MMVEC p-eNOS蛋白及eNOS基因表达明显下调;合用MHBFC后明显逆转上述指标的下调。结论 MHBFC可能通过增加MMVEC PI3K、Akt磷酸化及PI3K、Akt基因表达,增加MMVEC eNOS蛋白磷酸化及eNOS基因表达,激活MMVEC eNOS-NO信号通路,从而逆转压力超负荷心室重构。Aim To observe the mechanism of Yulangsan monomers 17-methoxyl-7-hydroxy-benzene-furanchalcone(MHBFC)regulating myocardial microvascular endothelial cell(MMVEC)eNOS-NO signaling pathway in reversing pressure overload-induced ventricular remodeling rats.Methods The survival rats with narrowed abdominal aorta were randomly divided into sham operated group,model group,MHBFC 6 mg·kg^-1 group,MHBFC 12 mg·kg^-1 group,MHBFC 12 mg·kg^-1+Nω-nitro-L-arginine methyl ester hydrochloride(L-NAME)50 mg·kg^-1 group and L-NAME 50 mg·kg^-1 group.In the sham operated group,only the abdominal aorta was free and not narrowed.After grouping,each group was given the corresponding drug for six weeks.MMVEC was obtained by chemical digestion in left ventricular tissue,and MMVEC was identified by Dil-Ac-LDL phagocytosis.The gene expression of MMVEC eNOS,PI3K and Akt was detected by qPCR.The protein expression of MMVEC p-eNOS,p-PI3K and p-Akt was detected using Western blot.Results The protein expression of MMVEC p-eNOS,p-PI3K and p-Akt and the gene expression of MMVEC eNOS,PI3K and Akt significantly increased in MHBFC pretreatment group.The expression of MMVEC p-eNOS protein and the expression of eNOS gene were obviously down-regulated in L-NAME group,and the down-regulation of the above index was obviously reversed after the combination of MHBFC.Conclusions MHBFC may increase the phosphorylation of MMVEC eNOS protein and the expression of MMVEC eNOS gene by increasing the phosphorylation of PI3K and Akt proteins and the expression of PI3K and Akt genes in MMVEC,and activate the eNOS-NO signaling pathway in MMVEC,thereby reversing pressure overload-induced ventricular remodeling.

关 键 词：17-甲氧基-7-羟基-苯并呋喃查尔酮 压力超负荷 心室重构 心肌微血管内皮细胞 eNOS-NO PI3K/Akt 

分 类 号：R-332[医药卫生] R284.1