Chang Wenguang, Zhang Ming, Meng Zhaojie, Yu Yang, Yao Fan, Hatch Grant M, Chen Li
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China; Department of Pharmacology and Therapeutics, Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, DREAM Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6.
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Eur J Pharmacol. 2015 Dec 15;769:55-63. doi: 10.1016/j.ejphar.2015.10.043. Epub 2015 Oct 30.
Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy.
糖尿病性心肌病是2型糖尿病患者死亡的主要原因。黄连素是一种从传统中药中提取的异喹啉生物碱，其降血糖和降血脂作用使其成为治疗2型糖尿病的一种有前景的药物。我们研究了黄连素是否能改善高脂饮食和链脲佐菌素诱导的2型糖尿病大鼠的心脏功能，并减轻心脏肥大和纤维化，以及在体外是否能降低棕榈酸诱导的肥大H9c2细胞中肥大标志物的表达。用黄连素治疗糖尿病动物可部分改善心脏功能，并使空腹血胰岛素、空腹血糖、总胆固醇和甘油三酯水平恢复至对照组水平。此外，与对照组相比，用黄连素治疗糖尿病动物可增加心脏5'-腺苷单磷酸激活蛋白激酶（AMPK）和蛋白激酶B（AKT）的激活，并降低糖原合酶激酶3β（GSK3β）的激活。与对照组相比，用棕榈酸孵育H9c2细胞导致细胞肥大，α-肌球蛋白重链（α-MHC）表达降低，β-肌球蛋白重链（β-MHC）表达增加。用黄连素处理经棕榈酸孵育的H9c2细胞可减轻肥大，增加α-MHC表达并降低β-MHC表达。此外，用黄连素处理经棕榈酸孵育的H9c2细胞可增加AMPK和AKT的激活并降低GSK3β的激活。AMPK抑制剂化合物C的存在减弱了黄连素的作用。结果强烈表明，黄连素治疗可能对糖尿病性心肌病的发展具有保护作用。
