梓醇、马钱苷及其配伍干预AGEs-RAGE通路对糖尿病睾丸病变的保护作用研究  

The protective effects of catapol,loganin and their compatibility on diabetes induced testicular damage through inhibiting AGEs-RAGE pathway

作　　者：陈玉萍 焦妮 朱逸辉 丁网丽 刘梦雪 李新亮 许惠琴[4] CHEN Yu-ping;JIAO Ni;ZHU Yi-hui;DING Wang-li;LIU Meng-xue;LI Xin-liang;XU Hui-qin(Basic Medicine Dept,Jiangsu Vocational College of Medicine,Yancheng,Jiangsu 224005,China;Chemistry and Life Sciences Dept,Jinling College,Nanjing University,Nanjing 210089,China;Pharmaceutical Dept,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]江苏医药职业学院基础医学部,江苏盐城224005 [2]南京大学金陵学院化学与生命科学学院,江苏南京210089 [3]江苏省中医院药学部,210029 [4]南京中医药大学药学院,江苏南京210023

出　　处：《中国药理学通报》2020年第7期998-1005,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.81903879,81874359);江苏省高等学校自然科学研究面上项目(No.17KJB360003);江苏高校优势学科建设工程资助项目(No.JKLPSE201604);江苏省高等学校大学生创新训练项目(No.201810315066Y)。

摘　　要：目的研究梓醇、马钱苷及其配伍对糖尿病睾丸病变的保护作用及机制。方法采用KK-Ay自发性糖尿病小鼠模型和糖基化终末产物诱导小鼠精母细胞株(GC-2)损伤模型,分组干预,HE染色检测睾丸的病理改变;试剂盒法检测睾丸特异性标志酶、SOD活性和ATP、ROS水平;AO/EB染色法检测GC-2的凋亡;Western blot法测定AGEs-RAGE通路相关蛋白的表达。结果梓醇、马钱苷及其配伍均可改善糖尿病小鼠睾丸病理损伤,降低血糖,升高睾丸特异性标志酶活力,降低AGEs诱导的GC-2细胞凋亡率,改善氧化应激,配伍组改善效果较优,同时梓醇、马钱苷及其配伍可下调模型组睾丸组织、GC-2细胞的RAGE及其下游蛋白Nox4的表达、抑制p38MAPK磷酸化。结论梓醇、马钱苷及其配伍对糖尿病睾丸病变有明显的保护作用,配伍组药效优于单用组,其作用机制与干预AGEs-RAGE通路相关。Aim To study the protective effects of catapol,loganin and their compatibility on diabetic testicular lesions and its mechanisms.Methods KK-Ay spontaneous diabetes mousemodel and mouse spermatocyte cell line(GC-2)injury model induced by AGEs were used to determine the protective effects and mechanism.The pathological changes of testis were tested by HE staining.Testicular specific marker enzyme,SOD activity,ATP and ROS levels were detected by kit methods.The apoptosis of GC-2 was detected by AO/EB staining.The expression of AGEs-RAGE pathway related proteins was determined by Western blot.Results Catapol,loganin and their compatibility could improve the pathological changes of testis in diabetic mice,increase the activity of testis-specific marker enzymes,decrease the apoptosis rate of GC-2 cells induced by AGEs,and improve oxidative stress,while the compatibility group exhibited more excellent effects,meanwhile,catapol,loganin and their compatibility down-regulated the expression of RAGE and its downstream protein Nox4,inhibited p38MAPK phosphorylation in testicular tissue and GC-2 cells.Conclusions Catapol,loganin and their combination showed obvious protective effects on diabetic testicular lesions by inhibiting AGEs-RAGE pathway,and the effect of the combination group was more evident than that of the single use.

关 键 词：AGEs 马钱苷 梓醇 配伍 RAGE 糖尿病睾丸病变 

分 类 号：R-332[医药卫生] R282.71