Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
p300 đóng vai trò sinh học epigen ở đau thần kinh mãn tính thông qua hoạt động acetyltransferase của nó ở chuột sau chấn thương thắt nghẹt mãn tính (CCI)
Tóm tắt
Đau thần kinh gây hại cho sức khỏe con người; tuy nhiên, cơ chế bệnh sinh của nó vẫn còn chưa được hiểu rõ. Sự biểu hiện quá mức của các gen liên quan đến đau và tính nhạy cảm với đau tăng cao thường được quan sát trong đau thần kinh. Tầm quan trọng của các cơ chế epigen trong việc điều chỉnh sự biểu hiện của các gen vốn có tác dụng pro- hoặc anti-nociceptive đã được các nghiên cứu gần đây tiết lộ, và chúng tôi giả thuyết rằng coactivator phiên mã và acetyltransferase histone p300 (p300), như một phần của các cơ chế epigen trong điều chỉnh gen, có thể tham gia vào cơ chế bệnh sinh của đau thần kinh do chấn thương thắt nghẹt mãn tính (CCI) gây ra. Để kiểm nghiệm giả thuyết này, hai phương pháp khác nhau đã được sử dụng trong nghiên cứu này: (I) giảm biểu hiện p300 bằng RNA nhỏ tóc (shRNA) và (II) ức chế hóa học hoạt động acetyltransferase của p300 bằng chất ức chế nhỏ, C646. Sử dụng mô hình chuột CCI, chúng tôi phát hiện rằng biểu hiện p300 tăng lên trong tủy sống thắt lưng vào ngày thứ 14 sau CCI. Việc điều trị bằng shRNA p300 tiêm vào được giảm đã đảo ngược tình trạng đau cơ học và đau nhiệt do CCI gây ra, và ức chế sự biểu hiện của cyclooxygenase-2 (COX-2), một yếu tố liên quan đến đau thần kinh. Hơn nữa, C646, một chất ức chế acetyltransferase của p300, cũng làm giảm đau cơ học và đau nhiệt, đi kèm với sự ức chế biểu hiện COX-2 trong tủy sống. Các kết quả cho thấy rằng, thông qua hoạt động acetyltransferase của nó trong tủy sống sau CCI, p300 tham gia vào vai trò quan trọng trong đau thần kinh ở mức độ epigen. Việc ức chế p300, bằng cách sử dụng RNA can thiệp hoặc C646, có thể là một hướng triển vọng cho việc phát triển các liệu pháp mới trong điều trị đau thần kinh.
Từ khóa
#Đau thần kinh #p300 #cơ chế epigen #hoạt động acetyltransferase #chấn thương thắt nghẹt mãn tính #cyclooxygenase-2 #RNA can thiệp.Tài liệu tham khảo
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