Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes rats by inhibiting endothelial cell migration
Mechanism study published in Life Sciences (2020)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Hirudin reduces nephropathy microangiopathy in STZ-diabetic rats via inhibition of endothelial cell migration and abnormal angiogenesis — vascular renoprotection mechanism.
Почему это важно для гирудотерапии
Данное исследование изучало эффекты гирудина на почечную микроангиопатию у крыс с диабетом, индуцированным STZ, и в клубочковых эндотелиальных клетках (GEC) in vitro; было установлено, что гирудин снижает уровень сывороточного креатинина, Cys C, суточную протеинурию, отношение массы почек к массе тела и площадь клубочков, а также улучшает почечную патологию по данным окраски гематоксилином и эозином (HE). Гирудин удлинял протромбиновое время и активированное частичное тромбопластиновое время, снижал экспрессию белков VEGF и TM-1 в почечной ткани, ингибировал миграцию GEC и ангиогенез в условиях высокой концентрации глюкозы, а также модулировал сигнальные пути RhoA, p-MYPT1/MYPT1 и p-p38/p38. Данная работа релевантна для сферы ASH, поскольку она изучает влияние гирудина на микрососудистую патологию при диабетической нефропатии, включая его воздействие на параметры свёртывания крови. Однако исследование было проведено исключительно на модели диабета у крыс, индуцированного STZ, и в экспериментах с клетками in vitro; данные на людях или клинические данные не представлены.
Цитирование
Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes rats by inhibiting endothelial cell migration.
Pang X et al. · Life sciences, 2020
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
Добавлено в библиотеку ASH: May 27, 2026 · Последнее обновление сайта: 18 июня 2026 г.