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.
Highlights
Immunoglobulin A nephropathy (IgAN) is the most common type of glomerulonephritis in the world [1]
Urine from rats was collected at 24 h, and it was observed that IgAN rats developed macroscopic hematuresis, the normal group and treatment group had no expression
The IgAN rat models showed significantly higher urine protein, blood urea nitrogen (BUN), and serum creatinine (Src) levels than the normal, healthy controls, whereas these were markedly lower in the treatment group (Figure 1)
Summary
Immunoglobulin A nephropathy (IgAN) is the most common type of glomerulonephritis in the world [1]. Oxford presented a new classification for IgA nephropathy as proposed by a Working Group of the International IgA Nephropathy Network and the Renal Pathology Society [13], which has been validated by numerous studies [14,15,16,17,18] This group identified four histopathologic features that are associated with the progression of kidney disease: mesangial hypercellularity score (M; M0 ≤ 0.5, M1 ≥ 0.5), the presence of endocapillary proliferation (E; E0: absent, E1: present), segmental glomerulosclerosis/adhesion (S; S0: absent, S1: present), and the severity of tubular atrophy/interstitial fibrosis (T; T0 ≤ 25%, T1: 26–50%, T2 ≥ 50%). This is the first study that has investigated the molecular mechanism of periostracum cicadae in inflammation and fibrosis using an IgAN model
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