基于蛋白质组学探讨羟基-α-山椒素对糖尿病心肌病的作用机制  

Study on mechanism of hydroxy-α-sanshool on diabetic cardiomyopathy based on proteomics

作　　者：王雪 黄硕 杨羚 肖雯婧 呼永河 WANG Xue;HUANG Shuo;YANG Ling;XIAO Wen-jing;HU Yong-he(School of Clinical Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China;the General Hospital of Western Theater Command,Chengdu 610083,China)

机构地区：[1]成都中医药大学临床医学院,四川成都610072 [2]中国人民解放军西部战区总医院,四川成都610083

出　　处：《中国药理学通报》2024年第3期537-544,共8页Chinese Pharmacological Bulletin

基　　金：四川省科技厅重点研发项目(No2020YFS0122);四川省中医药管理局专项任务(No2018HJZX013)。

摘　　要：目的基于蛋白质组学检测技术,探讨羟基-α-山椒素(hydroxy-α-sanshool,SAN)治疗糖尿病心肌病(diabetic cardiomyopathy,DCM)的作用机制。方法高脂饲料喂养及腹腔注射链脲佐菌素(streptozotocin,STZ)联合使用建立DCM模型。分为对照组(CON组)、DCM组和SAN治疗组(DCM+SAN组)。小动物心脏超声及病理染色评价小鼠心脏功能及组织形态,蛋白组学技术推测SAN对DCM的作用机制,Western blot实验验证cAMP/PKA信号通路关键蛋白表达水平。结果心脏超声与病理染色显示SAN对DCM小鼠心脏有保护作用。DCM+SAN组与DCM组进行蛋白组学检测,共鉴定160个差异蛋白,127个蛋白表达上调,33个蛋白表达下调;GO二级功能注释显示细胞过程、分子结构和细胞结构等功能;KEGG富集分析显示cAMP信号通路富集最为丰富;蛋白互作网络显示以PKA为中心节点与多种蛋白在cAMP信号通路中有互作关系。Western blot验证DCM组的cAMP和PKA蛋白相对表达量均明显低于CON组(P<0.05);DCM+SAN组的cAMP和PKA蛋白相对表达量均明显高于DCM组(P<0.05)。结论SAN对糖尿病心功能有保护作用,通过cAMP信号通路发挥作用。Aim To explore the mechanism of hydroxy-α-sanshool in the treatment of diabetic cardiomyopathy(DCM)based on label-free quantitative proteomics detection technique.Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin(STZ).They were divided into control group(CON group),diabetic cardiomyopathy group(DCM group)and hydroxy-α-sanshool treatment group(DCM+SAN group).The cardiac function of mice was evaluated by echocardiography,the myocardial morphology was observed by pathology staining,the protective mechanism of hydroxy-α-sanshool on diabetic cardiomyopathy was speculated by proteomic technique,and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting.Results Cardiac ultrasound and pathology staining showed that hydroxy-α-sanshool had protective effect on the heart of DCM mice.Label-free quantitative proteomic analysis was carried out between DCM+SAN group and DCM group,and 160 differential proteins were identified by proteomics,in which 127 proteins were up-regulated and 33 proteins were down regulated;GO secondary functional annotations showed the biological process,molecular function and cellular component;KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant;protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway.Western blot showed that the relative expression of cAMP,PKA protein in DCM group was significantly lower than that in CON group(P<0.05),while the relative expression of cAMP,PKA protein in DCM+SAN group was significantly higher than that in DCM group(P<0.05).Conclusions Hydroxy-α-sanshool has protective effect on heart function of mice with diabetes,which plays a role through cAMP signaling pathway.

关 键 词：蜀椒 羟基-α-山椒素 蛋白组学 糖尿病心肌病 作用机制 cAMP信号通路 

分 类 号：R-332[医药卫生] R282.71R341R394.3R542.2R587.2