Loại bỏ gen p66Shc liên quan đến sự trường thọ bảo vệ chống lại bệnh cầu thận do tiểu đường thí nghiệm bằng cách ngăn chặn stress oxy hóa do tiểu đường

Diabetes - Tập 55 Số 6 - Trang 1642-1650 - 2006
Stefano Menini1, Lorena Amadio2, Giovanna Oddi2, Pier Carlo Ricci1, Carlo Pesce3, Francesco Pugliese1, Marco Giorgio4, Enrica Migliaccio4, Pier Giuseppe Pelicci4, Carla Iacobini2, Giuseppe Pugliese1
1Department of Clinical Sciences, “La Sapienza” University, Rome, Italy
2Department of Cell Biology and Neurosciences, National Institute of Health of Italy, Rome, Italy
3DISTBIMO, University of Genoa Medical School, Genoa, Italy
4Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.

Tóm tắt

p66Shc điều chỉnh cả sản xuất các loài oxy phản ứng (ROS) phụ thuộc vào trạng thái ổn định và căng thẳng môi trường. Việc loại bỏ nó đã được chứng minh là giúp kháng lại stress oxy hóa và bảo vệ chuột khỏi bệnh mạch máu liên quan đến lão hóa. Nghiên cứu này nhằm xác minh giả thuyết rằng việc loại bỏ p66Shc cũng bảo vệ khỏi bệnh cầu thận do tiểu đường bằng cách giảm stress oxy hóa. Chuột p66Shc knockout (KO) tiểu đường do streptozotocin gây ra cho thấy những thay đổi ít rõ rệt hơn trong chức năng và cấu trúc thận, như được chỉ ra bởi các mức độ protein niệu, albumin niệu, chỉ số xơ hóa cầu thận và diện tích cầu thận và tế bào kẽ thấp hơn một cách đáng kể. Nội dung fibronectin và collagen IV ở cầu thận cũng thấp hơn ở chuột KO tiểu đường so với chuột kiểu hoang dã, trong khi apoptosis chỉ được phát hiện ở chuột kiểu hoang dã tiểu đường. Các sản phẩm cuối glycosyl hóa tiên tiến trong huyết thanh và mô thận, cũng như mức isoprostane 8-epi-prostaglandin F2α và kích hoạt yếu tố nhân κB (NF-κB) cũng thấp hơn ở chuột KO tiểu đường so với chuột kiểu hoang dã. Các tế bào kẽ từ chuột KO phát triển dưới điều kiện glucose cao cho thấy tỷ lệ chết tế bào, sản xuất matri, mức ROS và kích hoạt NF-κB thấp hơn so với các tế bào từ chuột kiểu hoang dã. Những dữ liệu này hỗ trợ vai trò của stress oxy hóa trong bệnh sinh của bệnh cầu thận do tiểu đường và chỉ ra rằng p66Shc liên quan đến cơ chế phân tử liên quan đến stress oxy hóa do tiểu đường gây ra và tổn thương thận phụ thuộc vào oxy hóa.

Từ khóa


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