小檗碱对实验性2型糖尿病心肌病大鼠模型心脏保护作用研究  

Berberine attenuates cardiac dysfunction in experimental type 2 diabetic cardiomyopathy rat model

作　　者：董世芬[1] 洪缨[1] 汪瑞祺[2] 于海食[1] 刘明[3] 孙建宁[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]安徽医科大学第一附属医院,安徽合肥230022 [3]贵阳中医学院,贵州贵阳550002

出　　处：《中国药理学通报》2013年第9期1216-1221,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30840103);北京中医药大学青年教师专项计划(No 2012-QNJSZX006)

摘　　要：目的研究小檗碱(berberine)对实验性2型糖尿病心肌病(diabetic cardiomyopathy,DC)大鼠模型心脏的保护作用,并探讨作用机制。方法高糖高脂膳食负荷小剂量链脲佐菌素(streptozotocin,STZ)诱导实验性2型DC大鼠模型,观察小檗碱对模型动物心脏功能、结构变化以及血浆、心肌组织糖脂代谢相关指标的作用。结果小檗碱治疗6周后,可明显改善DC大鼠模型心脏收缩和舒张功能,降低左心室前壁厚度、室间隔厚度以及心肌组织胶原含量;另外,小檗碱可减少模型动物血糖、血脂以及心脏游离脂肪酸(nonesterified fatty acids,NEFA)含量,增加心肌组织脂肪酸跨膜转运载体蛋白(fatty acid transporters,FATPs)和脂肪酸β氧化酶(fatty acidβoxidase,FA-β-oxidase)含量。结论小檗碱可改善糖尿病心肌病心脏舒张和收缩功能,抑制心肌肥厚和心室重构,作用机制可能与降低高血糖和高血脂状态、以及增加FATPs和FA-β-oxidase改善心肌内脂肪酸代谢紊乱有关。Aim To investigate protective effects of berberine on cardiac dysfunction in experimental type 2 diabetic cardiomyopathy （DC） rat model, and to ex- plore potential mechanisms. Methods The type 2 DC rat model was induced by intraperitoneal （i. p. ） injec- tion of a small dose of streptozotocin （ STZ, 30 mg · kg-1） plus high sucrose-high fat diet. After 6-week treatment of berberine （at the thirteenth week） , chan- ges of left ventricular systolic pressure （LVSP） , left ventricular end diastolic pressure （LVEDP） , the maxi- mum rate of myocardial contraction （ ＋ dp/dt ） and the maximum rate of myocardial diastole （ - dp/dtmax ） were detected using MP150 systems. The left ventricu- lar wall thickness （LVWT） and interventricular septum thickness （IST） were measured by Image-Proplus 5.0 image analysis software on hematoxylin and eosin slices microscopically. Levels of fasting blood sugar and lip- ids as well as myocardial nonesterified fatty acids （NE- FA） and collagen were determined using ultraviolet spectrophotometric method. Meanwhile, the concentra- tion of myocardial fatty acid transport proteins （FATPs） and fatty acid β oxidase （FA-β-oxidase） was measured by ELISA method. Results The systol- ic and diastolic function was significantly improved with the treatment of berberine for 6 weeks, when compared with the drug-untreated rats of DC. Meanwhile, when compared with DC rat model, the parameters of LVWT, IST and myocardial collagen content were sig- nificantly decreased. Levels of plasma sugar and lipids as well as myocardial NEFA were remarkably de- creased after the treatment of berberine, when com- pared with DC rats. In addition, berberine caused a significant increase in concentration of myocardial FATPs and FA-^-oxidase in DC rat model. Conclu- sion Our results indicate that berberine exerts protec- tive effects on cardiac dysfunction and hypertrophy through alleviating circulating and cardiac metabolic disorders.

关 键 词：小檗碱 糖尿病心肌病 血糖 血脂 游离脂肪酸 脂肪酸跨膜转运载体蛋白 脂肪酸β氧化酶 

分 类 号：R-332[医药卫生] R284.1