柚皮苷激活Maxi K对糖尿病心脏的保护作用  

The protective effect of naringin on cardiac injury in diabetic rats via activating Maxi K

作　　者：肖雯婧 邓凯文 王婷婷[2] 呼永河 侯君 XIAO Wen-jing;DENG Kai-wen;WANG Ting-ting;HU Yong-he;HOU Jun(Dept of Pharmacy,The General Hospital of Western Theater Command of PLA,Chengdu 610083,China;College of Medicine,Southwest Jiaotong University,Chengdu 610031,China)

机构地区：[1]中国人民解放军西部战区总医院药剂科,四川成都610083 [2]西南交通大学医学院,四川成都610031

出　　处：《中国药理学通报》2022年第1期38-42,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金项目(No 81900339,81402507);四川省科技厅重点研发项目(No 2018SZ0033);四川省卫健委重点项目(No 19ZDXM0016)。

摘　　要：目的探讨柚皮苷(naringin, NA)通过激活大电导钙激活钾离子通道(the large conductance Ca;activated K;channels, Maxi K)对糖尿病心肌病的保护作用。方法高脂饲料喂养SD大鼠,随后腹腔注射链脲佐菌素(streptozotocin, STZ)建立糖尿病大鼠模型。造模后随机分为模型组(DCM),柚皮苷治疗组(NA),柚皮苷+Maxi K特异性抑制剂治疗组(NA+PAX),每组8只大鼠。治疗组大鼠连续给药12周,定期检测血糖。结束后观察大鼠心功能、形态及纤维化改变;并检测心脏Maxi K的α及β亚基变化。结果超声显示NA可部分恢复大鼠心功能,而特异性阻断Maxi K后,NA对心脏的保护作用明显下降;纤维化分析显示NA治疗后可降低大鼠胶原蛋白及纤连蛋白表达,该作用可被PAX部分逆转;而Western blot结果显示Maxi Kα及β亚基在DCM组表达下降,NA治疗后无明显改变。结论柚皮苷通过促进细胞膜表面Maxi K通道开放而非增加其表达产生对糖尿病大鼠的心脏保护作用。Aim To investigate the protective effect of naringin(NA) on diabetic cardiomyopathy by activating the large conduction Ca;activated K;channels(Maxi K).Methods SD rats were fed with high-fat diet combined with intraperitoneal injection of streptozotocin(STZ) to establish a diabetic rat model. Then the rats were randomly divided into model group(DCM), naringin group(NA) and naringin + Maxi K-specific inhibitor group(NA+PAX), with 8 rats in each group. Rats in treatment group received administration for 12 weeks and blood glucose was monitored regularly during experiments. The changes of cardiac function, morphology and fibrosis were detected after the treatment. The changes of α and β subunits of Maxi K in heart were detected.Results Cardiac ultrasound results showed that NA could partially restore the cardiac function of rats. However, the cardiac protective function of NA was significantly reduced in diabetic rats after Maxi K was specifically blocked. Fibrosis analysis showed that the expression of collagen and fibronectin in rats could be decreased after NA treatment, which could be partially reversed by PAX. Western blot results showed that the expression of Maxi K α and β-subunit decreased in DCM group, but there was no significant change after NA treatment.Conclusions NA has a cardioprotective effect on diabetic rats by promoting the opening of the Maxi K channel on the membrane surface rather than increasing its expression.

关 键 词：柚皮苷 糖尿病心肌病 大电导钙激活钾离子通道 心肌纤维化 心肌重构 离子通道激活剂 

分 类 号：R-332[医药卫生] R284.1