The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus
The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus
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DOI：
10.1007/s10557-015-6629-y
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发表时间：
2015-12-01
影响因子：
3.4
通讯作者：
Fukagawa, Masafumi
中科院分区：
文献类型：
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作者：
Fujii, Hideki;Nakai, Kentaro;Fukagawa, Masafumi
目的最近的报道显示维生素D水平与心血管疾病事件和死亡率之间存在显著的相关性。本研究观察维生素D受体激动剂最大钙化醇(OCT)对2型糖尿病大鼠心脏损伤的影响。方法将20周龄的2型糖尿病大鼠随机分为3组：赋形剂组(DM)、胰岛素组(INS)和OCT组(OCT)。30周后处死大鼠，进行尿液和血液生化分析、心脏组织学和免疫组织化学分析。为了评估OCT对肾素-血管紧张素系统的影响，我们使用阿利吉伦(ALS)进行了进一步的研究。20周时，糖尿病大鼠分为ALS治疗组(ALS)和ALS+OCT治疗组(ALS+OCT)，在30周时检测肾素-血管紧张素系统(RAS)和心脏病变。结果30周时，尽管血压和肾功能相似，心脏体积、心脏内氧化应激、心脏及血管周围纤维化程度、8-羟基脱氧鸟苷排泄量和血清N-末端脑利钠肽原水平均显著低于DM组。与DM组相比，OCT组大鼠心脏二氢烟酰胺腺嘌呤二核苷酸磷酸(NADPH)P47亚单位和心肌损伤相关标志物的mRNA表达也明显降低。OCT的心脏保护作用即使在RAS抑制的情况下也能保持。结论OCT可预防糖尿病心脏损害的发展，而不依赖RAS抑制。
Purpose Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes.Methods At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS+OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks.Results At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition.Conclusion Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.