米非司酮对胰岛素抵抗大鼠儿茶酚胺含量的影响及可能机制

Effect and possible mechanism of mifepristone on catecholamine content in rats with insulin resistance

目的探讨米非司酮对胰岛素抵抗(IR)大鼠儿茶酚胺(CA)含量的影响及可能机制。方法 32只SD大鼠随机均分为空白对照组(A组)、模型对照组(B组)、米非司酮低剂量组(20mg.kg-1.d-1,C组)、米非司酮高剂量组(40mg.kg-1.d-1,D组)。高糖高脂饮食喂养大鼠8周后建立IR模型,通过胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR)等指标评估胰岛素的敏感性,同时检测血清皮质酮、血清、下丘脑和脑干CA含量及脑干、下丘脑中丙二醛(MDA)、超氧化物歧化酶(SOD)的变化。结果与A相比,B组大鼠HOMA-IR、血压、血清皮质酮、CA及MDA含量显著增加,ISI、SOD活性下降(P<0.05或P<0.01);而C、D组能明显改善B组上述指标的变化(P<0.05或P<0.01)。结论 IR状态下,交感活性增强引起的血压升高可能与机体氧化应激有关。米非司酮可能通过减少糖皮质激素引起的氧化应激,从而降低CA的含量和IR下高血压的发生。

Objective To investigate the effect and possible mechanism of mifepristone on catecholamine（CA） content in rats with insuin resistance（IR）. Methods Thirty-two SD rats were equally randomized into four groups of A（normal controls）, B（IR model）, C（treated with mifepristone 20 mg·kg^-1·d^-1 ） and D（treated with mifepristone 40 mg·kg^-1·d^-1 ）. The IR models in groups of IR and C were established by feeding high-sugar and high-fat diet（HSF） for eight weeks. The insulin sensitivity index（ISI） and IR index（HOMA-IR） were used to evaluate the insulin sensitivity. The contents of serum corticosterone,CA in serum, the hypothalamus and brain stem and the changes of malondialdehyde（MDA） and superoxide dismutase（SOD） in the brain stem and hypothalamus were detected. Results Compared with group A, the HOMA-IR, blood pressure and contents of serum corticosterone,CA and MDA were significantly increased, whereas the ISI and SOD activities were decreased in group B（P〈0. 05 or P〈0. 01） ,which were all obviously improved in groups of C and D （P〈0. 05 or P〈0. 01）. Conclusion Under IR condition, the increased oxidative stress（OS） may be related to hypertention induced by enhanced sympathetic activity. Mifepristone decreases CA content and blood pressure probably via attenuating glucocorticoid-induced OS.