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Iranian Journal of Basic Medical Sciences، جلد ۲۷، شماره ۳، صفحات ۳۴۳-۳۵۱
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عنوان انگلیسی Metformin alleviates bevacizumab-induced vascular endothelial injury in mice through growth differentiation factor 15 upregulation
چکیده انگلیسی مقاله Objective(s): Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects.Materials and Methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues.Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P<0.05). Metformin up-regulated GDF15 expression and PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05). siGDF15 abolished the vascular protective and anti-inflammatory effects of metformin (all P<0.05). siGDF15 suppressed PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05).Conclusion: Metformin attenuates bevacizumab-induced vascular endothelial injury, apoptosis, and systemic inflammation by activating GDF15/PI3K/AKT/FOXO/PPARγ signaling.
کلیدواژه‌های انگلیسی مقاله Bevacizumab, Growth differentiation-factor 15, Metformin, Mouse, PI3K/AKT/FOXO/PPARγ-, Signaling pathway, Vascular injuries
نویسندگان مقاله | Liqiang Chen
Department of Cardiovascular, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China


| Yajuan Yin
Department of Cardiovascular, The First Hospital of Hebei Medical University, Shijiazhuang, China


| Chunmiao Liu
Department of Obstetrics,The Fourth Hospital of Shijiazhuang,Shijiazhuang, China


| Junying Liu
Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China


| Mingqi Zheng
Department of Cardiovascular, The First Hospital of Hebei Medical University, Shijiazhuang, China


| Yida Tang
Department of Cardiology, Peking University Third Hospital, 49 Huayuanbei Road, Haidian District, Beijing 100191, China


| Qing Yang
Department of Cardiology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China


| Jing Liu
Department of Cardiovascular, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China


| Fan Chen
Department of Cardiovascular, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China


| Lanbo Liu
Department of Cardiovascular, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China


| Gang Liu
Department of Cardiovascular, The First Hospital of Hebei Medical University, Shijiazhuang, China
نشانی اینترنتی https://ijbms.mums.ac.ir/article_23350.html
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