La hirudina reduce la microangiopatía nefropática en ratas con diabetes inducida por STZ al inhibir la migración y angiogénesis de células endoteliales

OBJECTIVE: Kidney is the most common location of microangiopathy in diabetic patients, and we designed this study to investigate the effects of hirudin on renal microangiopathy in STZ-induced diabetes rats and in vitro. METHODS: We established a diabetes model by intraperitoneal injection of STZ and administered hirudin daily by subcutaneous injection. HE staining was used to assess kidney pathological changes. Western blot and immunochemistry was used to detect the protein expression. Glomerular endothelial cells (GEC) in normal rats were assessed by cell scratch test for migration ability and tubule formation experiment for angiogenesis ability. RESULTS: Compared with DN rats without any treatment, the serum creatinine, serum Cys C, 24-hour urine protein of DN rats with hirudin treatment were significantly decrease, the kidney/body weight and glomerular area of DN rats with hirudin treatment were all significantly decrease, and also significant improvement in renal pathology revealed by HE staining in DN rats after treating with hirudin. Moreover, we also found that hirudin coun not only significantly increase the prothrombin time and aivated partial thromboplastin time in DN rats, but also significantly decrease the expression of VEGF and TM-1 protein in kidney tissues of DN rats. In vitro, we found that high glucose could promote the migration and angiogensis of GEC, and significantly increased the expression of VEGF and Ang protein, but significantly decreased the expression of THBS1 and Arg1 protein. More importantly was that hirudin could inhibit the migration and angiogensis of GEC, and reversed HG-induced the expression of VEGF, Ang, THBS1 and Arg1 protein in GEC. In addition, we also found that hirudin could not only decrease HG-enhanced the activity of RhoA in GEC, but also decrease HG-enhanced the expression of p-MYPT1/MYPT1, p-p38/p38 protein in GEC. CONCLUSION: Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes, and might be related to hirudin inhibiting glomerular endothelial cell migration and angiogenesis through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

En ratas diabéticas por STZ, la hirudina subcutánea diaria redujo significativamente la creatinina, la cistatina C, la proteinuria de 24 h, el peso riñón/cuerpo y el área glomerular. Prolongó el tiempo de protrombina y la TTPa y disminuyó VEGF y TM-1 renales. In vitro inhibió la migración y la angiogénesis de células endoteliales glomerulares ante glucosa alta y revirtió la expresión de VEGF, Ang, THBS1 y Arg1. Según los autores, el efecto podría implicar las vías Rho-quinasa y p38MAPK/NF-κB.

Explore cómo esta investigación se conecta con la práctica clínica

Más estudios revisados por pares en la categoría «Genómica y proteómica».

• Leech Salivary Proteome and Transcriptome: 434 Deduced Protein Sequences — Liu Z, Tong X, Su Y, et al. (2019)
• Medicinal Leech Draft Genome — Anticoagulant Gene Survey — Kvist S, Manzano-Marín A, de Carle D, Trontelj P, Siddall ME (2020)
• La terapia con sanguijuelas (Hirudo medicinalis) atenúa las lesiones testiculares inducidas por isquemia/reperfusión testicular en un modelo animal — Davoodi F et al. (2021)
• Nueva proteína anticoagulante de la sanguijuela medicinal — Manuvera V et al. (2024)
• AIF-1 y RNASET2 desempeñan papeles complementarios en la respuesta inmunitaria innata de la sanguijuela medicinal — Baranzini N et al. (2019)
• Los péptidos antimicrobianos de la sanguijuela medicinal carentes de toxicidad representan una estrategia alternativa prometedora para combatir patógenos resistentes a antibióticos — Grafskaia E et al. (2019)
• Perspectivas estructurales sobre la actividad trombolítica de la destabilasa de la sanguijuela medicinal — Marin E et al. (2023)
• El genoma de la sanguijuela medicinal (Whitmania pigra) y un estudio genómico comparativo para la exploración de ingredientes bioactivos — Tong L et al. (2022)
• El SNC de la sanguijuela medicinal como modelo para estudios de exosomas en la comunicación cruzada entre microglía y neuronas — Raffo-Romero A et al. (2018)
• Transcriptomic profiling and the first spatial expression analysis of candidate genes in the salivary gland of the East Asian medicinal leech, Hirudo nipponia — Kim J et al. (2024)

Ver toda la investigación analizada por la ASH →