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. 2022 Jul 26:15:2183-2195.
doi: 10.2147/DMSO.S368867. eCollection 2022.

Yishen Capsule Alleviated Symptoms of Diabetic Nephropathy via NOD-like Receptor Signaling Pathway

Ziyuan Zhang  1   2 , Yaling Hu  1   2 , Wenyuan Liu  2 , Xiaodong Zhang  2 , Ruihua Wang  2 , Hui Li  2 , Dalin Sun  1   2 , Jingai Fang  2
Affiliations

Yishen Capsule Alleviated Symptoms of Diabetic Nephropathy via NOD-like Receptor Signaling Pathway

Ziyuan Zhang et al. Diabetes Metab Syndr Obes. .

Abstract

Purpose: To explore the mechanism of Yishen capsule against diabetic nephropathy (DN) based on the analysis of transcriptomics.

Material and methods: SD rats (Male, SPF grade) were randomly divided into four groups, the normal group, the DN group, the Yishen capsule group and the resveratrol group. Urine and renal tissue samples were collected after feeding with physiological saline and above drugs for 8 weeks. 24-hour urine microalbumin protein was detected by ELISA. HE staining and PAS staining were performed on renal tissues. Differential gene expression in renal tissues was analyzed by transcriptome sequencing. The differentially expressed genes were analyzed by GO enrichment and KEGG enrichment, and verified by RT-PCR and immunohistochemistry staining.

Results: The level of 24-hour urinary microalbumin in DN group was increased, while Yishen capsule treatment reversed the increasement of urinary microalbumin. Mesangial cell proliferation, matrix accumulation, edema and vacuolar degeneration of renal tubular epithelial cells and glycogen accumulation were observed in DN group. However, pathological phenotypes mentioned above were alleviated after Yisen capsule administration. This result indicates that Yishen capsule reversed pathological phenotypes of DN in rats. The expression of 261 genes were changed in Yishen capsule group compared with DN group. GO enrichment analysis and KEGG pathway analysis showed that these genes were implicated in pathways, including mineral absorption, adipocytokine signaling pathway, fatty acid biosynthesis, thyroid hormone synthesis, renin-angiotensin system, and NOD-like receptor signaling pathway. Based on previous reported study, the expression of key factors in NOD-like receptor signaling pathway was verified. RT-PCR and immunohistochemistry staining showed that the expression of NLRP3, Caspase-1 and IL-1β in renal tissues of DN group were increased (P < 0.05), which were decreased in Yishen capsule group (P < 0.05).

Conclusion: Yishen capsule reduced microalbuminuria and alleviated pathological changes in DN rats, which may be achieved by regulating NOD-like receptor signaling pathway.

Keywords: NOD-like receptor signaling pathway; Yishen capsule; diabetic nephropathy; transcriptome sequencing.

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Conflict of interest statement

The authors report no conflicts of interest in relation to this work.

Figures

Figure 1
Figure 1
Effect of Yishen capsule on 24-hour urinary microalbumin and pathological changes of kidney. (A) The level of 24-hour urinary microalbumin in each group. (B) Histopathological changes in each group. (*P < 0.05. Black arrows represent glycogen expression. Red arrows represent edema and vacuolar degeneration of renal tubular epithelial cells and mesangial cell proliferation, matrix accumulation).
Figure 2
Figure 2
Differentially expressed genes (DEGs) of the normal group versus DN group and YS group. (A) The volcano map of 321 DEGs between the normal group and DN group. (B) The volcano map of 261 DEGs between DN group and YS group. (C) Hierarchical clustering analysis of kidney samples between normal group, DN group and YS group, from 3 independent rats. The abscissa represents the log2FoldChange, and the ordinate indicates -log10 (p-value) of gene expression between the two groups. Up-regulated genes were red dots and down-regulated genes were blue dots.
Figure 3
Figure 3
Functional and pathway enrichment analysis of DEGs among the different groups of rats. (A) GO enrichment analysis of DEGs in the normal group of rats compared with DN rats. (B) GO enrichment analysis of DEGs in DN group of rats compared with YS group rats.
Figure 4
Figure 4
KEGG enrichment analysis for DEGs identified by transcriptomics analysis. (A) KEGG enrichment analysis for DEGs between the normal group and DN group. (B) KEGG enrichment analysis for DEGs between DN group and YS group.
Figure 5
Figure 5
Effect of Yishen capsule on NOD like receptor signaling pathway. (A) Immunohistochemistry staining for NLRP3, caspase-1 and IL-1β (×400). (B) The mRNA expression of NLRP3, caspase-1 and IL-1β. (*P < 0.05. Red arrows indicate the expression of target proteins detected by immunohistochemistry, with brown particles in glomerular, renal tubular epithelial cells).
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References

    1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi:10.1016/j.diabres.2019.107843 - DOI - PubMed
    1. Samsu N, Bellini MI. Diabetic nephropathy: challenges in pathogenesis, diagnosis, and treatment. Biomed Res Int. 2021;2021:1497449. doi:10.1155/2021/1497449 - DOI - PMC - PubMed
    1. Du X, Liu J, Xue Y, et al. Alteration of gut microbial profile in patients with diabetic nephropathy. Endocrine. 2021;73(1):71–84. doi:10.1007/s12020-021-02721-1 - DOI - PubMed
    1. Ni L, Yuan C, Wu X, Veljkovic A. Endoplasmic reticulum stress in diabetic nephrology: regulation, pathological role, and therapeutic potential. Oxid Med Cell Longev. 2021;2021:7277966. doi:10.1155/2021/7277966 - DOI - PMC - PubMed
    1. Davies MJ, D′Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669–2701. doi:10.2337/dci18-0033 - DOI - PMC - PubMed

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