Effects of Periostracum Cicadae on Cytokines and Apoptosis Regulatory Proteins in an IgA Nephropathy Rat Model

Int J Mol Sci. 2018 May 29;19(6):1599. doi: 10.3390/ijms19061599.

Abstract

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL (TdT-mediated dUTP Nick-End Labeling), and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by Western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1 (Monocyte Chemotactic Protein-1), TLR4 ((Toll-Like Receptor 4)), and IgA expression levels and a dose-dependent increase in caspase 3 expression were observed in response to periostracum cicadae treatment. TGF-β1(Transforming Growth Factor-β) levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

Keywords: IgA nephropathy; apoptosis; fibrosis; inflammation; periostracum cicadae.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Complex Mixtures / chemistry
  • Complex Mixtures / pharmacology*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Glomerulonephritis, IGA* / drug therapy
  • Glomerulonephritis, IGA* / metabolism
  • Glomerulonephritis, IGA* / pathology
  • Hemiptera / chemistry*
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Apoptosis Regulatory Proteins
  • Complex Mixtures
  • Cytokines