Early intervention with Didang decoction delays macrovascular lesions in diabetic rats through regulating AMP-activated protein kinase signaling pathway  

作　　者：REN Dan-Dan LI Jing CHANG Bai LI Chun-Shen YANG Ju-Hong 

机构地区：[1]Metabolic Diseases Hospital, Tianjin Medical University, Tianjin 300070, China [2]Tanggu Dahua Hospital, Tianjin Coastal New Area, Tianjin 300455, China [3]Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

出　　处：《Chinese Journal of Natural Medicines》2017年第11期847-854,共8页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81473622 and 81273914)

摘　　要：The study aimed to investigate the intervening role of Didang decoction(DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase(AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells(RAECs). Type 2 diabetes were induced in rats by streptozotocin(STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1(AMPKα1) and peroxisome proliferator-activated receptor 1α(PGC-1α). Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the m RNA level of caspase-3, endothelial nitric oxide synthase(eNOS), and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group(P< 0.05). The levels of Bcl-2, eNOS, and ATP were significantly increased(P<0.05), while the level of AMP and caspase-3 were decreased(P< 0.05) in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.The study aimed to investigate the intervening role of Didang decoction（DDD） at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase（AMPK） signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells（RAECs）. Type 2 diabetes were induced in rats by streptozotocin（STZ） combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1（AMPKα1） and peroxisome proliferator-activated receptor 1α（PGC-1α）. Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the m RNA level of caspase-3, endothelial nitric oxide synthase（eNOS）, and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group（P〈 0.05）. The levels of Bcl-2, eNOS, and ATP were significantly increased（P〈0.05）, while the level of AMP and caspase-3 were decreased（P〈 0.05） in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.

关 键 词：Didang DECOCTION Caspase-3 AMPK ENDOTHELIAL cells PGC-1Α 

分 类 号：R965[医药卫生—药理学]