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Cyanidin-3-glucoside ức chế ferroptosis trong tế bào ống thận sau tổn thương thiếu máu/có lại (ischemia/reperfusion) thông qua con đường AMPK
Tóm tắt
Ferroptosis, đặc trưng bởi sự oxy hóa lipid và tích tụ sắt, có mối liên quan chặt chẽ với quá trình bệnh sinh của tổn thương thận cấp tính (AKI). Cyanidin-3-glucoside (C3G), một flavonoid điển hình với tác dụng chống viêm và chống oxy hóa đối với tổn thương thiếu máu/có lại (I/R), có khả năng kích hoạt protein kinase AMP (AMPK). Nghiên cứu này nhằm chứng minh rằng C3G có tác dụng bảo vệ thận chống lại ferroptosis liên quan đến I/R-AKI bằng cách điều chỉnh con đường AMPK. Các tế bào HK-2 bị kích thích bởi thiếu oxy/khi tái oxy hóa (H/R) và chuột I/R-AKI được điều trị với C3G với hoặc không có ức chế AMPK. Chúng tôi đã kiểm tra mức sắt tự do trong tế bào, sự biểu hiện của các protein liên quan đến ferroptosis là acyl-CoA synthetase long chain family member 4 (ACSL4) và glutathione peroxidase 4 (GPX4), cũng như các chỉ số oxy hóa lipid như 4-hydroxynonenal (4-HNE), các loài oxy phản ứng lipid (ROS) và malondialdehyde (MDA). Chúng tôi quan sát thấy tác dụng ức chế ferroptosis của C3G cả in vitro và in vivo, được đặc trưng bởi sự đảo ngược tích tụ sắt tự do quá mức trong tế bào, sự giảm thiểu của 4-HNE, lipid ROS, mức MDA và sự biểu hiện ACSL4, cũng như sự gia tăng biểu hiện GPX4 và mức glutathione (GSH). Đáng chú ý, việc ức chế AMPK bằng CC đã làm giảm đáng kể tác dụng bảo vệ thận của C3G trên các mô hình I/R-AKI cả in vivo và in vitro. Kết quả của chúng tôi cung cấp cái nhìn mới về tác dụng bảo vệ thận của C3G đối với I/R-AKI cấp tính bằng cách ức chế ferroptosis thông qua việc kích hoạt con đường AMPK.
Từ khóa
#ferroptosis #tổn thương thận cấp tính #Cyanidin-3-glucoside #AMPK #oxy hóa lipid #AKITài liệu tham khảo
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