Yoshifuji Ayumi, Wakino Shu, Irie Junichiro, Matsui Ayumi, Hasegawa Kazuhiro, Tokuyama Hirobumi, Hayashi Koichi, Itoh Hiroshi
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Clin Exp Nephrol. 2018 Oct;22(5):1069-1078. doi: 10.1007/s10157-018-1577-z. Epub 2018 Apr 19.
Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment.
Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact.
The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects.
AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.
据报道，口服活性炭吸附剂AST-120（AST）可通过吸收肠道中的有毒物质来改善肾功能障碍。最近的研究表明，在慢性肾脏病（CKD）中，肠道环境受到干扰，包括紧密连接和乳酸杆菌（Lact）数量减少。在本研究中，我们研究了AST是否通过肠道环境改善肾功能障碍。
六周龄自发性高血压大鼠（SHR）通过5/6肾切除术（Nx）诱导成为CKD。SHR分为SHR（假手术组）、Nx诱导的SHR（Nx组）和给予AST的Nx诱导的SHR（Nx + AST组）（每组n = 10）。12周后，处死大鼠并检测生化指标。分析肠道菌群。此外，检测紧密连接和Toll样受体的肠道分子变化。我们还研究了AST与Lact联合治疗的效果。
Nx + AST组恢复了Nx组血清尿素氮和尿蛋白排泄的增加。Nx + AST组改善了Nx组增加的肾小球硬化。Nx + AST组改善了Nx组血清尿毒症毒素和IL-6的增加。肠道菌群分析显示，Nx + AST组恢复了Nx组Lact的减少。AST减轻了Nx组紧密连接和TLR2的下调。然而，联合治疗未显示出额外的效果。
AST通过TLR途径恢复Lact和紧密连接，改善肾功能，减轻全身炎症，发挥肾脏保护作用。我们的研究提供了AST肾脏保护作用的新机制。
