褪黑素对胰岛素抵抗大鼠肾皮质内皮素、内皮型一氧化氮合酶平衡的影响

目的 研究褪黑素对胰岛素抵抗(IR)大鼠肾皮质内皮素1(ET-1)、内皮型一氧化氮合酶(eNOS)表达的影响.方法 高糖饲料喂养SD大鼠6周复制IR大鼠模型.成模后用药组(MEL组)予褪黑素10mg·kg-1·d-1灌胃,用药6周.未用药IR大鼠模型为对照(IR组).免疫组化、RT-PCR方法 检测肾皮质ET-1、eNOS蛋白和mRNA表达的改变.结果 与IR组相比,褪黑素组大鼠动脉血压(ABP)、血清TG、游离脂肪酸(FFA)、丙二醛(MDA)、胰岛素(Ins)和HOMA-IR降低(P＜0.01),血清HDL-c、超氧化物歧化酶(SOD)升高(P＜0.01).HE染色MEL组大鼠肾皮质病变明显减轻.MEL组ET-1蛋白及mRNA明显低于IR组、eNOS蛋白及mRNA明显高于IR组,差别均有显著意义(P＜0.05).结论 在IR早期应用褪黑素(10mg·kg-1·d-1)治疗可以减轻IR大鼠肾皮质ET-1与eNOS平衡的异常,对肾皮质血管内皮功能具有一定保护作用.

Effect of melatonin on the balance of ET-1 and eNOS in the renal cortex of insulin-resistant rats

Objective To study the effects of melatonin on the expression of endothelin-1 (ET-1) and endothelial nitricoxide synthase (eNOS) in renal cortex of insulin-resistant (IR) rats. Methods Insulin-resistant rat model was established with 6-8 week ages Sprague-Dawwley (SD) rats by high-glucose diet (70% calories from glucose) for 6 weeks. IR rats models were divided into control normal group (CN, n=10), IR group (n=10) and melatonin group (MEL, n=10). Rats in MEL were affused melatonin 10mg/(kg·d) (4PM) for further 6 weeks. The protein and mRNA in rats' renal cortex of each group were assayed by immunohistochemistry and RT-PCR. Results Arterial blood pressure (ABP) and serum triglyceride (TG), free fatty acid (FFA), malondialdehyde (MDA), insulin (Ins) and homeostasis model analysis insulin resistance (HOMA-IR) in MEL were lower than that in IR (all P＜0.01). Serum high-density lipoprotein (HDL-c) and superoxide dismutese (SOD) were higher in MEL than that in IR (all P＜0.01). HE staining showed that the structure of renal cortex in MEL is approximately normal. The levels of ET-1 protein and mRNA in renal cortex of MEL rats were lower than that in IR group. The levels of eNOS protein and mRNA of renal cortex in MEL group were higher than that in IR group (all P＜0.05). Conclusion At the early stage of IR, melatonin application can ameliorate the imbalance between ET-1 and eNOS and protect the angio-endothelial function of renal cortex in high-glucose induced IR rats.