苦参碱对自发性高血压大鼠心肌肥厚的作用及机制研究  

Effect Mechanism of Matrine on the Myocardial Hypertrophy in Spontaneously Hypertensive Rats

作　　者：魏明慧 鲁子瑜 李建英 卢孔秦 任中杰 尹东杰 薛明明 WEI Minghui;LU Ziyu;LI Jianying;LU Kongqin;REN Zhongjie;YIN Dongjie;XUE Mingming(Medical Research Public Service Center,Inner Mongolia Medical University,Hohhot 010110,China;School of Basic Medicine,Inner Mongolia Medical University,Hohhot 010110,China)

机构地区：[1]内蒙古医科大学医学科研公共服务中心,内蒙古呼和浩特010110 [2]内蒙古医科大学基础医学院,内蒙古呼和浩特010110

出　　处：《现代中药研究与实践》2025年第1期23-32,共10页Research and Practice on Chinese Medicines

基　　金：国家自然科学基金项目(82360095);内蒙古自治区自然科学基金(2022LHMS08002);自治区卫生健康科技计划项目(202201221);内蒙古自治区科技计划项目(2020GG0238)。

摘　　要：目的探讨苦参碱(Mat)对自发性高血压大鼠(SHR)氧化应激和心肌肥厚的分子机制,以及其对活化转录因子6(ATF6)/蛋白激酶B(Akt)信号的调控机制。方法动物实验分为SHR组(SHR)、Mat组(Mat)、激活剂组(740Y-P)、抑制剂组(GSK-690693),每组10只;以10只WKY大鼠作为正常对照组(Control);TUNEL检测细胞凋亡率;试剂盒检测血清SOD和MDA的水平;Rh123染色检测线粒体膜电位,DHE检测活性氧自由基(ROS)的水平;Western blot检测ATF6、Akt、磷酸化Akt(p-Akt)、淋巴细胞瘤-2(Bcl-2)和Bcl-2相关x蛋白(Bax)的表达。结果Mat能明显降低心肌组织的细胞凋亡率,降低血清中MDA水平,升高SOD的水平,上调心肌组织线粒体膜电位,降低心肌组织中ROS水平;Mat能明显降低p-Akt、Bax的表达,升高ATF6、Bcl-2的表达;740Y-P可部分逆转Mat对动物心肌组织的保护作用,GSK-690693可部分解除740Y-P的逆转作用,差异均具有统计学意义(P<0.05)。结论Mat能明显抑制SHR大鼠心肌组织的氧化应激和细胞凋亡,改善动物的心功能,这可能与调控ATF6/Akt信号的表达有关。Objective To investigate?the molecular mechanism of matrine(Mat)in reducing oxidative stress and myocardial hypertrophy in spontaneously hypertensive rats(SHR),as well as its regulatory mechanism on activating transcription factor 6(ATF6)/protein kinase B(Akt)signaling pathway.Methods The animal experiments were divided into SHR group(SHR),Mat group(Mat),activator group(740Y-P),and inhibitor group(GSK-690693),with 10 mice in each group,another 10 WKY rats were set as the normal control group.TUNEL assay was used to detect cell apoptosis in rat myocardial tissue.Enzyme linked adsorption assay kit was used to detect the levels of SOD and MDA in rat serum.Rh123 staining was used to detect the mitochondrial membrane potential.DHE was used to detect the level of reactive oxygen species(ROS).Western blot assay was used to detect the expression of ATF6,Akt,phosphorylated Akt(p-Akt),B cell lymphoma-2(Bcl-2)and Bcl-2 associated x protein(Bax).Results Mat could significantly reduce cell apoptosis rate in myocardial tissue,downregulate serum MDA level,increase SOD level,upregulate mitochondrial membrane potential in myocardial tissue,reduce ROS level in myocardial tissue.Mat could significantly reduce the expression of p-Akt and Bax,and increase the expression of ATF6 and Bcl-2.740Y-P could partially reverse the protective effect of Mat on animal myocardial tissue,while GSK-690693 could partially relieve the reversal effect of 740Y-P,the differences were statistically significant(P<0.05).Conclusion Mat can significantly inhibit oxidative stress in myocardial tissue of SHR rats,reduce cell apoptosis rate in myocardial tissue,improve animal heart function,which may be related to regulating the expression of ATF6/Akt signaling pathway.

关 键 词：苦参碱 自发性高血压 氧化应激 心肌肥厚 活化转录因子6/蛋白激酶B信号 

分 类 号：R285.5[医药卫生—中药学]