Hypertension is associated with gut dysbiosis and dysregulation of the gut–brain axis. Previous work has shown that probiotic treatments exert beneficial cardiovascular effects in humans and animal models of hypertension. Coupled with the evidence of elevated sympathetic outflow and chronic inflammation in hypertension, we hypothesized that both peripherally and centrally mediated mechanisms underlie the antihypertensive effects of kefir, a probiotic obtained from the fermentation of milk by kefir grains. Eight-week-old spontaneously hypertensive rats (SHRs) were treated by oral gavage with either vehicle or kefir (0.3 ml/100 g/day; 9 weeks; SHR-Kefir), and age-matched with vehicle-treated Wistar Kyoto rats (WKY). Long-term kefir treatment attenuated mean arterial pressure elevations in SHR-Kefir relative to vehicle-treated SHRs. Peripherally, SHRs exhibited differences in the wall of the jejunum (fewer Paneth cells per crypt of Lieberkϋhn and increased tunica muscularis thickness) and higher serum lipopolysaccharide levels compared to WKY, alterations which were reversed in SHR-Kefir. Centrally, kefir treatment reduced IL-6 and TNF-α protein densities, and abolished the microglial activation observed in the hypothalamic paraventricular nucleus and rostral ventrolateral medulla of SHRs. Taken together, our findings indicate that the antihypertensive effects of long-term kefir treatment occur, at least in part, through improved structural and functional integrity of the intestinal wall and protection against neuroinflammation within cardioregulatory nuclei.

高血压与肠营养不良和肠脑轴失调有关。先前的工作表明，益生菌治疗对高血压的人和动物模型具有有益的心血管作用。结合高血压中交感神经外流增加和慢性炎症的证据，我们假设外周和中央介导的机制都是开菲尔的降压作用的基础，开菲尔是通过开菲尔谷物发酵牛奶而获得的益生菌。对八周大的自发性高血压大鼠（SHR）进行口服灌胃或媒介或开菲尔（0.3 ml / 100 g /天； 9周； SHR-Kefir）的治疗，并与媒介治疗的Wistar Kyoto大鼠进行年龄匹配（ WKY）。相对于媒介物治疗的SHR，长期开菲尔治疗可减轻SHR-Kefir中平均动脉压升高。外围地 与WKY相比，SHRs在空肠壁上表现出差异（每个Lieberkϋhn隐窝的Paneth细胞更少，肌膜厚度增加）和更高的血清脂多糖水平，这种变化在SHR-Kefir中得到了逆转。从中央来看，开菲尔治疗降低了SHRs的下丘脑室旁核和延髓腹侧延髓中观察到的小胶质细胞激活，并降低了IL-6和TNF-α蛋白的密度。综上所述，我们的发现表明，长期开菲尔治疗的抗高血压作用至少部分是通过改善肠壁的结构和功能完整性以及防止心脏调节核内神经炎症而发生的。