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低聚果糖富集菊粉对腺嘌呤诱导的慢性肾病大鼠肠道来源尿毒症毒素及疾病进展的影响。

Effects of prebiotic oligofructose-enriched inulin on gut-derived uremic toxins and disease progression in rats with adenine-induced chronic kidney disease.

机构信息

Nutrition and Dietetics Department, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey.

Laboratory Animals Application and Research Center, Hacettepe University, Ankara, Turkey.

出版信息

PLoS One. 2021 Oct 6;16(10):e0258145. doi: 10.1371/journal.pone.0258145. eCollection 2021.

DOI:10.1371/journal.pone.0258145
PMID:34614017
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8494360/
Abstract

Recent studies suggest that dysbiosis in chronic kidney disease (CKD) increases gut-derived uremic toxins (GDUT) generation, leads to systemic inflammation, reactive oxygen species generation, and poor prognosis. This study aimed to investigate the effect of oligofructose-enriched inulin supplementation on GDUT levels, inflammatory and antioxidant parameters, renal damage, and intestinal barrier function in adenine-induced CKD rats. Male Sprague-Dawley rats were divided into control group (CTL, n = 12) fed with standard diet; and CKD group (n = 16) given adenine (200 mg/kg/day) by oral gavage for 3-weeks to induce CKD. At the 4th week, CKD rats were subdivided into prebiotic supplementation (5g/kg/day) for four consecutive weeks (CKD-Pre, n = 8). Also, the control group was subdivided into two subgroups; prebiotic supplemented (CTL-Pre, n = 6) and non-supplemented group (CTL, n = 6). Results showed that prebiotic oligofructose-enriched inulin supplementation did not significantly reduce serum indoxyl sulfate (IS) but did significantly reduce serum p-Cresyl sulfate (PCS) (p = 0.002) in CKD rats. Prebiotic supplementation also reduced serum urea (p = 0.008) and interleukin (IL)-6 levels (p = 0.001), ameliorated renal injury, and enhanced antioxidant enzyme activity of glutathione peroxidase (GPx) (p = 0.002) and superoxide dismutase (SOD) (p = 0.001) in renal tissues of CKD rats. No significant changes were observed in colonic epithelial tight junction proteins claudin-1 and occludin in the CKD-Pre group. In adenine-induced CKD rats, oligofructose-enriched inulin supplementation resulted in a reduction in serum urea and PCS levels, enhancement of the antioxidant activity in the renal tissues, and retardation of the disease progression.

摘要

最近的研究表明,慢性肾脏病(CKD)中的菌群失调会增加肠道来源的尿毒症毒素(GDUT)的产生,导致全身炎症、活性氧物质的产生和预后不良。本研究旨在探讨富含低聚果糖的菊粉补充剂对腺嘌呤诱导的 CKD 大鼠 GDUT 水平、炎症和抗氧化参数、肾损伤和肠道屏障功能的影响。雄性 Sprague-Dawley 大鼠分为对照组(CTL,n = 12),给予标准饮食;和 CKD 组(n = 16),通过口服灌胃给予腺嘌呤(200mg/kg/天),持续 3 周以诱导 CKD。第 4 周时,CKD 大鼠分为连续 4 周补充益生元(5g/kg/天)的亚组(CKD-Pre,n = 8)。此外,对照组分为补充益生元(CTL-Pre,n = 6)和未补充组(CTL,n = 6)。结果表明,益生元低聚果糖富集菊粉补充剂并没有显著降低血清吲哚硫酸(IS),但确实显著降低了 CKD 大鼠的血清对甲酚硫酸(PCS)(p = 0.002)。益生元补充还降低了血清尿素(p = 0.008)和白细胞介素(IL)-6 水平(p = 0.001),改善了 CKD 大鼠的肾损伤,并增强了肾脏组织中谷胱甘肽过氧化物酶(GPx)(p = 0.002)和超氧化物歧化酶(SOD)(p = 0.001)的抗氧化酶活性。在 CKD-Pre 组中,结肠上皮紧密连接蛋白 Claudin-1 和 Occludin 没有观察到明显变化。在腺嘌呤诱导的 CKD 大鼠中,富含低聚果糖的菊粉补充剂可降低血清尿素和 PCS 水平,增强肾脏组织的抗氧化活性,并延缓疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/677842d49249/pone.0258145.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/c64778ecbd4b/pone.0258145.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/5195a4d3a253/pone.0258145.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/3128c01eea49/pone.0258145.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/677842d49249/pone.0258145.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/c64778ecbd4b/pone.0258145.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/5195a4d3a253/pone.0258145.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/3128c01eea49/pone.0258145.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d4/8494360/677842d49249/pone.0258145.g004.jpg

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