Wang Lei, Zhu Qing, Lu Aihua, Liu Xiaofen, Zhang Linlin, Xu Chuanming, Liu Xiyang, Li Haobo, Yang Tianxin
aInstitute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China bVeterans Affairs Medical Center, University of Utah, Salt Lake City, Utah, USA.
J Hypertens. 2017 Sep;35(9):1899-1908. doi: 10.1097/HJH.0000000000001378.
Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism.
Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean arterial blood pressure was recorded by the telemetry system. Renal tissues, serum samples, and 24-h urine samples were collected to examine renal injury and the regulation of the (pro)renin receptor (PRR) and renin.
Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced mean arterial pressure from 129 ± 6 mmHg to 108 ± 4 mmHg (P < 0.01). This corresponded with an improvement in Ang II-induced renal injury, including urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the expression of inflammatory mediators tumor necrosis factor α, interleukin 6. The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and the urinary excretion of soluble PRR, renin, and angiotensinogen were all increased by Ang II infusion but decreased by NaBu treatment. In cultured innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced expression of PRR and renin.
These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.
丁酸盐是一种短链脂肪酸，是肠道微生物群对复杂碳水化合物发酵的终产物。最近，已发现丁酸钠（NaBu）在多种慢性疾病中发挥保护作用。然而，NaBu在高血压中是否具有治疗潜力仍不清楚。本研究旨在探讨NaBu在血管紧张素II（Ang II）诱导的高血压中的作用，并进一步探索其潜在机制。
将Ang II注入单侧肾切除的Sprague-Dawley大鼠体内，有或没有髓内注入NaBu，持续14天。通过遥测系统记录平均动脉血压。收集肾组织、血清样本和24小时尿液样本，以检查肾损伤以及（前）肾素受体（PRR）和肾素的调节情况。
在Sprague-Dawley大鼠中髓内注入NaBu可使Ang II诱导的平均动脉压从129±6 mmHg降至108±4 mmHg（P<0.01）。这与Ang II诱导的肾损伤改善相对应，包括尿白蛋白、肾小球硬化和肾纤维化，以及炎症介质肿瘤坏死因子α、白细胞介素6的表达。Ang II注入可增加PRR、血管紧张素原、血管紧张素I转换酶的肾表达以及可溶性PRR、肾素和血管紧张素原的尿排泄，但NaBu治疗可使其降低。在培养的髓质集合管细胞中，NaBu治疗减弱了Ang II诱导的PRR和肾素表达。
这些结果表明，NaBu可能通过抑制PRR介导的肾内肾素-血管紧张素系统发挥降压作用。
