摘要
目的:研究褪黑素对胰岛素抵抗(IR)大鼠心肌血管内皮的作用。方法:复制IR大鼠模型,成模后用药组(Mel组)予褪黑素10 mg·kg-1·d-1灌胃,用药6周。未用药IR大鼠模型为对照(IR组)。检测各组大鼠代谢及氧化指标,观察心室肌组织学变化,免疫组化、RT PCR方法检测心室肌内皮素1(ET 1)、内皮型一氧化氮合酶(eNOS)蛋白、mRNA表达的改变。结果:与IR组相比,Mel组大鼠收缩压(SBP)、血清三酰甘油(TG)、游离脂肪酸(FFA)、丙二醛(MDA)、胰岛素(Ins)降低(P<0.01),胰岛素敏感指数(ISI)、超氧化物歧化酶(SOD)、血清高密度脂蛋白胆固醇(HDL c)升高(P<0.01);H E染色Mel组大鼠心肌病变明显减轻;Mel组ET 1蛋白及mRNA表达量明显低于IR组,eNOS蛋白及mRNA表达量明显高于IR组,均有显著差别(P<0.05)。结论:在IR早期应用褪黑素(10 mg·kg-1·d-1)治疗可改善IR大鼠心肌血管内皮功能异常。
Objective:To study the protective effect of melatonin on myocardial angioendothelial function of insulin-resistant rats. Methods: An insulin-resistant(IR) animal model was reproduced in Sprague-Dawley(SD) rats aged 6-8 weeks. The animals were fed with high-glucose diet ( 70% calories from glucose) for 6 weeks. IR rats were divided into IR control group (n=10) and melatonin (Mel) group(n=10). Rats in Mel group were intragastered with melatonin at 10 mg·kg -1·d -1 (4:00 PM) for 6 weeks.In both groups, systolic blood pressure(SBP) was measured; serum triglyceride(TG),free fatty acid(FFA), malondialdehyde(MDA), insulin(Ins),high-density lipoprotein-cholesterol(HDL-c) and superoxide dismutese(SOD) were determined; and insulin sensitivity index(ISI) was calculated.Histologic change of the myocardium was observed.The protein and mRNA in the myocardium rats were assayed by immunohistochemistry and RT-PCR. Results: SBP and serum TG,FFA, MDA and Ins in Mel group were lower than those in IR group (P<0.01).Serum HDL-c, SOD, and ISI were higher in Mel group than those in IR group(P<0.01). H-E stain showed that the pathologic changes of the myocardium in Mel group were attenuated compared with IR group(P<0.05). The levels of ET-1 protein and mRNA of the myocardium in Mel group were lower than those in IR group(P<0.05). The levels of eNOS protein and mRNA of the myocardium in Mel group were higher than those in IR group( P<0.05). Conclusion: Melatonin application can at the early stage of IR ameliorate the abnormal balance between ET-1 and eNOS and protect the angioendothelial function of the myocardium in high-glucose induced IR rats.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2005年第4期406-410,共5页
Academic Journal of Second Military Medical University
基金
上海市医学发展基金重点项目资助课题[2001ZD002(3)].
关键词
褪黑素
胰岛素抵抗
血管内皮
内皮素1
内皮型一氧化氮合酶
心肌
melatonin
insulin resistance
angioendothelium
endothelin-1
endothelial nitricoxide synthase
myocardium
