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The Characteristics of Intestinal-Barrier Damage in Rats With IgA Nephropathy
Nan Zhou1, Ying Shen1, Lirong Fan2
1Department of Nephrology,; National Center for Children's Health (Beijing), Beijing, China; Key Laboratory of Chronic Kidney Disease and Blood Purification in Childhood (Beijing), Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.
Background:
Intestinal-barrier damage plays an important pathogenic role in immunoglobulin A nephropathy (IgAN). In this study, we explored the characteristics of the intestinal barrier in rats with IgAN.
Materials And Methods:
We randomly divided 17 Sprague Dawley (SD) male rats into a normal control group (NC; n = 9) and an IgAN model group (n = 8). Feces in the distal ileum were taken for intestinal-microbiota 16sDNA sequencing. We also took a segment of terminal ileum to analyze intestinal morphology and to detect mRNA and protein expression of the tight-junction proteins zonula occludens-1 (ZO-1) and occludin (OCLN), as well as of mucin 2 (MUC2). We then measured levels of serum diamine oxidase (DAO) and D-lactic acid (D-LA), the biomarkers of intestinal permeability.
Results:
Compared with the NC group, mRNA expression levels of ZO-1 (t = 4.216, P = 0.0007), OCLN (t = 2.413, P = 0.029) and MUC2 (t = 0.859, P < 0.0001) were significantly decreased in the IgAN model group. Protein expression of ZO-1 (t = 7.349, P < 0.0001) and OCLN (t = 6.367, P < 0.0001) was also decreased in the IgAN model group. Conversely, serum DAO (t = 3.758, P = 0.0024) and D-LA (t = 2.246, P = 0.0427) levels increased in this group. At the genus level, the relative abundance of Ruminococcus2 (P = 0.0086) was increased in the IgAN model group.
Conclusions:
Decreased expression of ZO-1, OCLN and MUC2, plus intestinal-microbiota dysbiosis, are associated with intestinal-barrier damage in IgAN rats.
