Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats.
Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats.
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DOI：
10.1007/s10157-018-1577-z
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发表时间：
2018-10
影响因子：
2.3
通讯作者：
Itoh H
中科院分区：
文献类型：
--
作者：
Yoshifuji A;Wakino S;Irie J;Matsui A;Hasegawa K;Tokuyama H;Hayashi K;Itoh H
据报道，口服活性炭吸附剂AST-120（AST）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CKD中，肠道环境受到干扰，包括紧密连接和乳杆菌（Lactobacillus）的减少。在这项研究中，我们研究了AST是否通过肠道环境改善肾功能不全。6周龄自发性高血压大鼠（SHR）通过第5/6肾切除术（Nx）造成CKD。SHR分为SHR（Sham）、Nx（Nx）和Nx + AST（Nx + AST）组，每组10只。12周后处死大鼠，检测生化指标。分析肠道植物群。此外，检查了紧密连接和Toll样受体的肠道分子变化。我们还研究了AST和Lact联合治疗的效果。Nx组血清尿素氮和尿蛋白排泄量的增加在Nx + AST组恢复。Nx + AST组肾小球硬化程度减轻。在Nx + AST中，Nx中血清尿毒症毒素和IL-6的增加得到改善。肠道植物群分析显示，Nx中Lact的降低在Nx + AST中得到恢复。AST可减轻Nx中紧密连接和TLR 2的下调。然而，联合治疗未能表现出额外的效果。AST可通过TLR途径恢复Lact和紧密连接，减轻全身炎症反应，发挥肾脏保护作用。本研究为AST的肾脏保护作用提供了新的机制。
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.
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DOI：
10.2147/ijnrd.s41339
发表时间：
2014
影响因子：
2
作者：
Schulman G;Vanholder R;Niwa T
通讯作者：
Niwa T
影响因子：
3.7
作者：
Shimada Y;Kinoshita M;Harada K;Mizutani M;Masahata K;Kayama H;Takeda K
通讯作者：
Takeda K
影响因子：
4.2
作者：
Vaziri ND;Yuan J;Khazaeli M;Masuda Y;Ichii H;Liu S
通讯作者：
Liu S
影响因子：
2.9
作者：
Schroeder, Jennifer C.;DiNatale, Brett C.;Murray, Iain A.;Flaveny, Colin A.;Liu, Qiang;Laurenzana, Elizabeth M.;Lin, Jyh Ming;Strom, Stephen C.;Omiecinski, Curtis J.;Amin, Shantu;Perdew, Gary H.
通讯作者：
Perdew, Gary H.
影响因子：
13.2
作者：
Akizawa, Tadao;Asano, Yasushi;Kurokawa, Kiyoshi
通讯作者：
Kurokawa, Kiyoshi