Berberine Pretreatment Confers Cardioprotection Against Ischemia-Reperfusion Injury in a Rat Model of Type 2 Diabetes
Berberine Pretreatment Confers Cardioprotection Against Ischemia-Reperfusion Injury in a Rat Model of Type 2 Diabetes
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DOI：
10.1177/1074248415627873
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发表时间：
2016-09-01
影响因子：
2.6
通讯作者：
Chen, Li
中科院分区：
文献类型：
--
作者：
Chang, Wenguang;Li, Kun;Chen, Li
临床前和临床研究表明，小檗碱（BBR）可改善糖尿病并发症，降低充血性心力衰竭患者的死亡率。据报道，BBR的治疗作用是通过调节腺苷一磷酸（AMP）活化的蛋白激酶（AMPK）介导的。我们以前报道过，BBR通过调节大鼠心脏缺血和非缺血区域的AMPK活性来保护缺血-再灌注损伤。由于糖尿病心脏对缺血再灌注损伤更敏感，我们研究了BBR治疗是否在糖尿病心脏中表现出心脏保护作用。2型糖尿病大鼠预处理+或-BBR 7天，并进行30分钟的缺血，然后再灌注120分钟。与未治疗的糖尿病对照组相比，用BBR预处理2型糖尿病大鼠可减少缺血再灌注损伤、梗死面积和减弱心律失常。缺血再灌注后，血清甘油三酯，总胆固醇和丙二醛水平降低2型糖尿病大鼠与未经处理的糖尿病对照组相比，BBR预处理。相反，血清葡萄糖和超氧化物歧化酶水平不变。研究了BBR介导的心脏保护作用的机制。与未经治疗的糖尿病对照组相比，BBR预处理未改变缺血风险区域的AMPK活性，但增加了非缺血区域的AMPK活性。非缺血区AMPK活性增加是由于AMP与三磷酸腺苷（ATP）和二磷酸腺苷与ATP的比值升高。此外，与未经治疗的糖尿病对照组相比，BBR预处理可增加非缺血区域的蛋白激酶B（AKT）磷酸化并降低糖原合成酶激酶3（GSK 3）活性。提示BBR对糖尿病心脏缺血再灌注损伤具有保护作用。此外，BBR可能通过AMPK激活、AKT磷酸化和糖尿病心脏非缺血区域的GSK 3抑制介导这种心脏保护作用。
Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia-reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. Since diabetic hearts are more sensitive to ischemia-reperfusion injury, we examined whether BBR treatment exhibited cardioprotective effects in the diabetic heart. Type 2 diabetic rats were pretreated plus or minus BBR for 7 days and subjected to 30-minute ischemia followed by 120-minute reperfusion. Pretreatment of type 2 diabetic rats with BBR reduced ischemia-reperfusion injury infarct size and attenuated arrhythmia compared to untreated diabetic controls. Subsequent to ischemia-reperfusion, serum triglyceride, total cholesterol, and malondialdehyde levels were reduced by pretreatment of type 2 diabetic rats with BBR compared to untreated diabetic controls. In contrast, serum glucose and superoxide dismutase levels were unaltered. The mechanism for the BBR-mediated cardioprotective effect was examined. Pretreatment with BBR did not alter AMPK activity in ischemic areas at risk but increased AMPK activity in nonischemic areas compared to untreated diabetic controls. The increased AMPK activity in nonischemic areas was due an elevated ratio of AMP to adenosine triphosphate (ATP) and adenosine diphosphate to ATP. In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3 (GSK3) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia-reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3 inhibition in the nonischemic areas of the diabetic heart.