Drug Design, Development and Therapy (2020-08-01)

Hirudin Protects Against Kidney Damage in Streptozotocin-Induced Diabetic Nephropathy Rats by Inhibiting Inflammation via P38 MAPK/NF-κB Pathway

  • Han J,
  • Pang X,
  • Zhang Y,
  • Peng Z,
  • Shi X,
  • Xing Y

Journal volume & issue
Vol. Volume 14
pp. 3223 – 3234


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Jiarui Han,1,2 Xinxin Pang,1,2 Yage Zhang,1,2 Zining Peng,1,2 Xiujie Shi,1,2 Yufeng Xing1,2 1Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Nephropathy, The Second Hospital Affiliated to Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Jiarui Han; Xinxin PangThe Second Hospital Affiliated to Henan University of Chinese Medicine, 6, Dong Feng Road, Jinshui District, Zhengzhou, Henan Province 450002, People’s Republic of ChinaTel +86-371-60979837Email [email protected]; [email protected]: Inflammation-induced podocyte apoptosis plays an important role in kidney injury during diabetic nephropathy (DN). Hirudin (HIR), a natural compound extracted from leeches, can inhibit inflammation. However, whether HIR can protect the kidneys against inflammation during DN is unknown. In the present study, we aimed to study the effects of HIR on kidney damage in a DN rat model and explore its anti-inflammatory properties.Methods: A streptozotocin-induced DN rat model was generated, and HIR was administered subcutaneously. Immortal podocytes and primary peritoneal macrophages were used for vitro studies. Hematoxylin and eosin staining was used to evaluate renal pathological changes; quantitative polymerase chain reaction and immunoblotting were used to detect gene expression; and TUNEL staining was used to detect apoptotic cells.Results: Our results showed that HIR protected against renal injury, as indicated by kidney weight/body weight, serum creatinine, renal pathological changes, blood urea nitrogen, and detection of urine proteins. Notably, HIR treatment reduced macrophage infiltration, pro-inflammatory cytokine expression, and podocyte apoptosis in the kidney tissues of DN rats. In vitro, high glucose (HG) induced the activation of M1 macrophages, which was accompanied by increased podocyte apoptosis. HIR could decrease HG-induced podocyte apoptosis and suppress pro-inflammatory cytokine expression in podocytes in vitro. This was achieved via inhibition of p38 MAPK/NF-κB activation in renal tissues and podocytes.Conclusion: HIR could inhibit inflammation via the p38 MAPK/NF-κB pathway, prevent podocyte apoptosis, and protect against kidney damage in a DN rat model.Keywords: hirudin, inflammation, apoptosis, diabetic nephropathy, kidney damage