游离脂肪酸减弱海马对HPA轴的负反馈调控

Elevated free fatty acid levels attenuate hippocampal negative feedback inhibition of HPA axis in rats

目的探讨短期血浆游离脂肪酸(FFA)升高是否通过改变海马11β-羟类固醇脱氢酶1(11β-HSD1)或诱导型一氧化氮合酶(i NOS)的表达,导致HPA轴的激活。方法将20只成年雌性SD大鼠分成两组,一组输注20%脂肪乳(FFA组,n=10),另一组输注0.9%生理盐水作为对照组(NS组,n=10)。输液3h后断头处死大鼠、取血、摘取海马。结果(1)输注脂肪乳能够激活HPA轴。(2)输注脂肪乳后海马CA4亚区锥体细胞的11β-HSD1 mRNA水平以及蛋白表达水平均明显减少。但是FFA组海马CA4亚区锥体细胞的i NOS mRNA水平以及蛋白表达水平却明显增加。(3)两组间糖皮质激素受体与盐皮质激素受体的mRNA水平以及蛋白表达水平无明显差异。结论提示FFA水平升高能够激活HPA轴,其激活机制可能与FFA下调海马局部11β-HSD1以及上调i NOS的表达,减弱了海马对HPA轴的抑制调控有关。

Objective To explore whether the activation of the HPA axis response to acute high free fatty acid（FFA） level was associated with the altered expression of iNOS and 11β-HSD1 in hippocampus. Methods After baseline sample was obtained,20% intralipid （FFA group, n= 10） or 0.9 % saline （as control, NS group,n= 10） was infused IV （2mL/h） into Sprague-Dawley rats for 180 min. Rats were killed by decapitation after infustion, trunk blood were collected,and hippocampus from animals were dissected. Results （1） Intralipid infusion activated the HPA axis. （2）In FFA group,11β-HSD1 mRNA and protein levels were significantly decreased in the pyramidal cells in hippocampal CA4 subregion compared with NS group. However,intralipid infusion significantly increased iNOS mRNA and protein levels in the pyramidal cells in the CA4 field of hippocampus. （3） There was no significant effect on GR/MR mRNA and protein levels in the hippocampal formation after intralipid infusion. Conclusion High circulating FFA levels activate the HPA axis in rats. The mechanism of the action of FFA might be attributable to down-regulation of 11β-HSD1 and up-regulation of iNOS expression in hippocampus.