American Society of Hirudotherapy

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis

Basic science / preclinical published in Cell biology and toxicology (2023)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Drug DevelopmentHan J et al. · Cell biology and toxicology, 2023

Abstract

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1β. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsRatsMiceAnimalsDiabetic NephropathiesHirudinsEndothelial CellsPyroptosisKidneyDiabetes Mellitus

Summary

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown.

Why This Matters for Hirudotherapy

This study investigated the mechanism by which hirudin ameliorates diabetic nephropathy, administering daily subcutaneous hirudin to streptozotocin-induced diabetic wild-type and Gasdermin D (Gsdmd)-knockout mice over 12 weeks and conducting parallel in vitro experiments on primary glomerular endothelial cells, renal tubular epithelial cells, and bone-marrow-derived macrophages. The authors report that hirudin reduced kidney injury by suppressing Gsdmd-mediated pyroptosis through inhibition of interferon regulatory factor 2 (Irf2), rather than via Caspase 1-mediated apoptosis. Hirudin is a key agent in hirudotherapy, and this work outlines a mechanistic pathway through which it may protect renal tissue. Relevance to clinical leech therapy is limited and indirect, however: the study used injected hirudin in rodent and cell-culture models—no leeches, leech saliva, or human subjects were involved—and findings remain preclinical.

Citation

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Han J et al. · Cell biology and toxicology, 2023

DOI

Added to ASH library: March 18, 2026 · Site last updated: June 18, 2026

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