《自然》子刊:变傻?可能是盐吃多了……

氯化钠




饮食中含有丰富的氯化钠(盐),是世界范围内发病率和死亡率的确切原因, 不同人群的开创性流行病学研究首先揭示了高盐摄入与高血压和心血管疾病之间的联系,但随后的研究证实,盐也有独立于血压升高的有害作用。

基于以上这些令人信服的证据,卫生组织发布了相关的建议,以限制盐摄入量。 然而,临床试验并没有明确显示这些干预措施对健康的益处,同时饮食盐损害大脑的机制还不清楚。因此,一度引发了民众对于限制盐摄入的有效性的科学证据的质疑,并呼吁进一步的研究,以更好地了解其在健康和疾病中的作用。


近期,发表在《自然》子刊《自然•神经科学》的一篇报道引起人们的关注。此研究发现: 过量的饮食盐抑制了小鼠的脑血流量和内皮功能,导致认知障碍。而此抑制效果取决于TH17淋巴细胞在小肠中的扩增,从而导致血浆白细胞介素-17(IL-17)的显着增加。反过来,循环中的IL-17通过Rho激酶依赖性抑制性内皮一氧化氮合酶磷酸化以减少内皮细胞中一氧化氮的产生到导致内皮功能障碍和认知障碍。

在此研究中,研究者在三个月的时间里给实验小鼠(HSD)喂食高出正常小鼠数倍的食盐量,然后通过检测脑部静息血流,发现高盐饮食使小鼠脑部血流降低了约25%-28%,与正常组小鼠有显著性差异,然后对各组小鼠进行了新物体,迷宫等实验以检测其认知水平,结果发现高盐饮食的小鼠的认知能力相对于正常组小鼠明显降低,同时,其筑巢本能也消失。但是,可喜的是,这种损害并不是不可逆的,研究者通过降低高盐饮食,发现曾高盐饮食小鼠脑部静息血流又明显下降。


这一发现揭示了一种与饮食有关的环境因素导致肠道适应性免疫反应,促进脑灌注不足,神经血管失调和认知障碍的一种新的肠脑轴,从而将饮食习惯与认知障碍联系起来。

因此,对TH17淋巴细胞IL-17途径的研究对于揭示针对饮食盐和与TH17极化相关的其它有害脑疾病具有重大意义,同时本项研究也对广大爱好重口味的民众起到警醒作用,为了更健康的生活,是时候调整自己的饮食习惯,吃点清淡的的啦。

原文:

Introduction

A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain. We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on expansion of TH17 cells in the small intestine, resulting in a marked increase in plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial dysfunction and cognitive impairment by the Rho kinase–dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells. The findings reveal a new gut–brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response compromising brain function via circulating IL-17. Thus, the TH17 cell–IL-17 pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated with TH17 polarization.


Abstract

We report that mice fed a high salt diet develop marked cerebral hypoperfusion and a profound alteration in the endothelial regulation of the cerebral microcirculation, leading to subsequent cognitive impairment. These effects depended on TH17 lymphocytes and were reproduced by recombinant IL-17 in mice fed a normal diet,pointing to their dependence on the HSD-induced TH17 response. The neurovascular and behavioral changes were mediated by suppression of endothelial NO by circulating IL-17, via Rho kinase (ROCK)-dependent inhibitory phosphorylation of endothelial NO synthase (eNOS). The findings unveil a gut–brain axis by which environmental factors linked to the diet lead to an adaptive immune response in the gut, promoting cerebral hypoperfusion, neurovascular dysregulation and cognitive impairment.


Results

• HSD reduces resting cerebral blood flow and induces endothelial dysfunction, effects reversed by return to a normal diet.

• HSD induces cognitive dysfunction.

• The NO precursor l-arginine reverses the neurovascular and cognitive dysfunction of HSD.

• HSD increases inhibitory eNOS phosphorylation.

• HSD induces TH17 differentiation in the small intestine and increases IL-17 plasma levels.

• The neurovascular and cognitive effects of HSD are not observed in mice lacking IL-17 or lymphocytes (Rag1−/− mice).

• The neurovascular and the cognitive effects of HSD are prevented by IL-17 neutralizing antibodies and reproduced by recombinant IL-17 in mice fed a normal diet.

• IL-17 induces ROCK-dependent increases in inhibitory eNOS phosphorylation and dampens endothelial NO production.

• ROCK inhibition ameliorates the neurovascular and cognitive dysfunction of HSD.


References

https://www.nature.com/articles/s41593-017-0059-z


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