关键词: 黄芪多糖, 肾功能衰竭, 慢性, RNA, 长链非编码；NF-κB, 胃肠道微生物组, 紧密连接蛋白质类, 长链非编码RNA Arid2-IR, 肠-肾轴

Abstract: Objective　To explore the protective effect of astragalus polysaccharide on chronic renal failure in mice and its potential molecular mechanism. Methods　The chronic renal failure mouse model was established by 5/6 nephrectomy in male Balb/c mice. They were randomly divided into the model group and astragalus polysaccharide intervention group (APS group) with 10 mice in each group. Another sham operation group was set up. After normal feeding for 7 weeks, the APS group was given astragalus polysaccharide 100 mg/(kg·d) gavage, and the remaining groups were given an equal volume of normal saline. Samples of stool, urine, blood, kidney and colon tissues were collected after 4 weeks. The creatinine (Scr), urea nitrogen (BUN) and 24 h urine protein were determined. After the tissues were fixed and embedded, the tissues were stained with HE and Sirius red for pathological analysis. Western blot assay and immunohistochemical staining were used to detect the tight junction protein-1 family (Claudin-1, Occludin-1, ZO-1) and p-NF-κB expression level. The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) concentration. The real-time fluorescent quantitative PCR was used to detect long-chain non compiled RNA (lncRNA) Arid2-IR, IL-1β, IL-6 and TNF-α expression changes and changes in the fecal flora of mice. Results　The blood Scr, BUN and 24 h urine protein were significantly decreased in the APS group than those of the model group. HE staining showed that the pathological damage of kidney and colon tissues were improved in the APS group compared with those of the model group. Sirius red staining showed that the degree of fibrosis was significantly improved in the APS group. Western blot assay and immunohistochemical staining showed that the expression of tight junction protein-1 family in colonic tissues was increased and the expression of p-NF-κB protein in renal tissues was decreased in the APS group compared with the model group. ELISA results showed that the levels of serum IL-1β, IL-6 and TNF-α were significantly decreased in the APS group compared with those of the model group. The relative expression levels of lncRNA Arid2-IR, IL-1β, IL-6 and TNF-α were significantly decreased in the APS group compared with those of the model group. The expression levels of lactic acid bacillus and bifidobacterium were higher in the APS group than those of the model group, while the relative expression level of E. coli decreased. Conclusion　Astragalus polysaccharide may regulate the intestinal flora of mice by regulating the lncRNA Arid2-IR/NF-κB signal axis, thereby repairing the intestinal barrier damage, maintaining the normal intestinal physiological environment and improving chronic renal failure.

Key words: ASTRAGALAN, kidney failure, chronic, RNA, long noncoding, NF-kappa B, gastrointestinal microbiome, tight junction proteins, lncRNA Arid2-IR, intestinal-renal axis