MiR-495 điều chỉnh sự phân cực của đại thực bào M1/M2 và kháng insulin ở chuột ăn chế độ ăn giàu chất béo thông qua việc nhắm vào FTO

Pflügers Archiv - Tập 471 - Trang 1529-1537 - 2019
Fang Hu1, Jingkai Tong2, Bangli Deng3, Jia Zheng1, Chengzhi Lu1
1Department of Cardiology, Tianjin First Central Hospital, Tianjin, China
2Department of Endocrinology, Tianjin First Central Hospital, Tianjin, China
3Clinical Laboratory of Metabolic Diseases Hospital of Tianjin Medical University, Tianjin, China

Tóm tắt

MicroRNA 495 (miR-495) đã được phát hiện có liên quan đến quá trình trao đổi chất và phản ứng miễn dịch trong cơ thể con người. Mục đích của nghiên cứu này là điều tra tác động của miR-495 đối với sự phân cực của đại thực bào M1/M2 và kháng insulin ở bệnh tiểu đường loại 2 (T2D). Mô hình chuột T2D đã được thiết lập bằng cách cho chuột C57BL/6 ăn chế độ ăn giàu chất béo (HFD). Các mức biểu hiện của các dấu hiệu phân cực M1/M2 và miR-495 trong các đại thực bào trong khoang bụng đã được xác định bằng qRT-PCR hoặc Western blot. Các bài kiểm tra dung nạp insulin (ITT) và dung nạp glucose (GTT) được thực hiện, và hiệu ứng liên kết mục tiêu giữa miR-495, khối lượng chất béo và gen liên quan đến béo phì (FTO) đã được xác minh bằng phương pháp xét nghiệm báo cáo gen luciferase kép. Cân nặng cơ thể, hàm lượng glucose trong máu và biểu hiện miR-495 trong các đại thực bào của nhóm HFD cao hơn đáng kể so với nhóm chế độ ăn bình thường (ND). Bên cạnh đó, miR-495 đã kích thích sự chuyển hóa của đại thực bào thành các đại thực bào pro-inflammatory M1 và làm tăng kháng insulin ở chuột T2D. Quan trọng hơn, FTO được chứng minh là một gen mục tiêu trực tiếp của miR-495 và sự làm im lặng FTO có thể thúc đẩy sự chuyển hóa của các đại thực bào thành các đại thực bào pro-inflammatory M1. Những kết quả này đã chứng minh rằng miR-495 có thể thúc đẩy sự chuyển hóa của đại thực bào thành các đại thực bào pro-inflammatory M1 bằng cách ức chế biểu hiện của gen mục tiêu FTO, và làm trầm trọng thêm tình trạng kháng insulin và viêm mô mỡ ở chuột T2D, từ đó cung cấp cơ sở lý thuyết nhất định cho việc điều trị nhắm mục tiêu bệnh tiểu đường loại 2.

Từ khóa

#miR-495 #đại thực bào M1/M2 #kháng insulin #chế độ ăn giàu chất béo #FTO #bệnh tiểu đường loại 2

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