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Abstract: TH-PO375

Rhein Reverses miR-34a-Mediated Autophagy in D-Galactose-Induced Renal Aging Rats via the Regulation of Gut Microbiome

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Tu, Yue, Nanjing University of Chinese Medicine, Nanjing, JIangSu, China
  • Liu, Buhui, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
  • Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China

Group or Team Name

  • Nanjing University of Chinese Medicine
Background

The alterations of gut microbiota in composition, diversity and functional features have a close relationship with aging-associated pathologies, including renal aging. microRNAs (miRNAs)-mediated autophagy also has an important role in aging. Recently, traditional Chinese herbal medications have been reported to possess potent anti-aging activities. Rhein is a bioactive constituent of rhubarb, derived from the root of Rheum palmatum with the anti-aging pharmacological effect. But the characteristics of gut microbiome and its relationship with miRNAs-mediated autophagy of rhein in anti-renal aging are unknown.

Methods

Forty rats were divided into Normal (N), Model (M), Rhein (R) and Vitamin E (VE) groups. D-galactose (D-gal) was used to induce renal aging. The appropriate doses of rhein, VE and distilled water were administrated with oral, respectively. All rats were sacrificed after 8 weeks treatments. Blood serum, fecal samples and kidneys were collected for the detection of various indicators. The characteristics of gut microbiome were determined by 16S rDNA Sequencing. Serum concentrations of uremic toxins indoxyl sulfate (IS), p-cresol sulfate (pCS) and trimethylamine oxide (TMAO) were detected by ELISA. miR-34a expression level was detected by RT-PCR. The senescence-associated-β-galactosidase (SA-β-gal) staining was observed. The aging-related protein expressions of Klotho, p53 and p21, as well as the protein expressions of autophagy markers, Beclin-1, LC3 I/II, p62, and Atg12 were detected by Western Blot.

Results

Results showed that, the structure and diversity of gut microbiota in 4 groups were different. Rhein and VE could reverse the abundance of some genus changed significantly in M group when compared with N group. Rhein and VE could notably decrease the increased IS, pCS and TMAO in M group. Rhein and VE markedly alleviated the up-regulation of miR-34a in M group. In addition, rhein and VE could attenuate strong positive staining for SA-β-gal, and reverse the significantly changed aging-related protein expressions and autophagy markers in M group.

Conclusion

This study proved rhein, similar to VE, could alleviate renal aging via regulating gut microbiome and miR-34a-mediated autophagy. Thus, targeting gut-kidney axis and miRNAs-mediated autophagy may provide new strategies in age-associated renal damage of the elderly patients.

Funding

  • Government Support - Non-U.S.